The dual roles of exosomes in prostate cancer: mechanisms in tumorigenesis and avenues for clinical translation

Prostate cancer (PCa) management remains challenged by tumor heterogeneity, unpredictable progression, and limitations in early detection, driving demand for innovative biological insights. As pivotal mediators of intercellular communication, exosomes exhibit dualistic roles in PCa pathogenesis and therapy. While acting as ‘foes’ by facilitating epithelial-mesenchymal transition (EMT), angiogenesis, tumor microenvironment formation, metastasis, immune evasion, and therapy resistance, they concurrently serve as ‘friends’ through their diagnostic and therapeutic potential. Exosome-derived biomarkers enable non-invasive liquid biopsy for early diagnosis, risk stratification, and treatment monitoring. Moreover, engineered exosomes function as targeted drug carriers, delivering precision therapeutics to overcome treatment barriers. This review systematically examines exosomal biogenesis, isolation methodologies, and their bidirectional regulation in PCa progression, while exploring emerging diagnostic and therapeutic applications to advance exosome-mediated precision oncology.

1 Introduction

Prostate cancer (PCa) ranks as the second most prevalent malignancy and fifth leading cause of cancer mortality among males globally, posing a significant clinical challenge for prevention and treatment (1). Early-stage localized PCa can be effectively managed with surgery or radiation therapy, leading to favorable prognoses. However, once the disease progresses to advanced metastatic or castration-resistant stages (Castration-Resistant Prostate Cancer, CRPC), treatment options become significantly limited, and patient survival is severely compromised (2). Investigating the underlying mechanisms of PCa development, metastasis, and drug resistance is crucial for developing novel diagnostic and therapeutic strategies and improve the prognosis of patients (3). Accumulating evidence underscores exosomes—critical intercellular mediators—as pivotal yet complex regulators of prostate cancer progression, orchestrating tumor microenvironment (TME) dynamics while shaping clinical therapeutic strategies.

Exosomes are 30–150 nm nanovesicles released by cells upon multivesicular body (MVB) fusion with the plasma membrane into the extracellular space (4). They carry cell-specific “molecular cargo,” including proteins, lipids, DNA, mRNA, and non-coding RNAs with crucial regulatory functions, such as miRNA, lncRNA, and circRNA (5). These bioactive molecules internalize into recipient cells via endocytosis or membrane fusion, mediating intercellular communication and modulating both physiological and pathological processes (5). Refined exosome isolation and characterization methodologies—including differential ultracentrifugation, size exclusion chromatography, and immunoaffinity purification—enable rigorous investigation of exosomal functions across diverse pathologies, particularly cancer (6).

Exosomes exhibit a notable “double-edged sword” characteristic in the complex pathogenesis of prostate cancer. On one hand, as accomplices of the tumor, exosomes secreted by prostate cancer cells serve as key drivers of malignant progression. They transmit signals that induce epithelial-mesenchymal transition (EMT), enhancing the invasion and migration capabilities of tumor cells; promote angiogenesis, providing nutritional support for tumor growth and dissemination; facilitate cancer cell metastasis; and contribute to the establishment of an immunosuppressive microenvironment, aiding tumor cells in evading immune clearance (7). Moreover, exosomes mediate drug resistance such as chemotherapy and targeted therapy has become an important source of clinical treatment failure. On the other hand, exosomes also demonstrate promising potential as “beacons of hope.” Ubiquitous in biofluids (e.g., blood, urine), exosomes encapsulate tumor-specific molecular signatures, thus establishing their utility as liquid biopsy targets. These vesicles serve as non-invasive tools for prostate cancer diagnosis, risk stratification, prognostic evaluation, and therapeutic response monitoring. Engineered exosomes exhibit innate biocompatibility, barrier-penetrating capability, and target specificity, positioning them as ideal nanocarriers. Their capacity to encapsulate chemotherapeutics, nucleic acid drugs (e.g., siRNA), and other nanotherapeutics enables development of precision oncology strategies with enhanced efficacy (8).

Exosomes play an extremely complex dual role in the field of prostate cancer: it is not only a key promoter of malignant evolution of tumors, but also a revolutionary diagnostic and therapeutic tool with great potential. A deeper understanding of the complex signaling networks mediated by exosomes and their bidirectional roles in prostate cancer is crucial, not only for a more comprehensive understanding of the disease’s nature and overcoming clinical challenges such as metastasis and drug resistance, but also for paving the way toward the development of exosome-based non-invasive diagnostics, precise prognostic assessments, and targeted therapies. This review will systematically discuss the fundamental biological characteristics of exosomes and their isolation and identification methods, with a particular focus on their dual roles in prostate cancer progression (mechanisms promoting tumor progression and their diagnostic and therapeutic applications). It will also explore the current challenges and future directions in exosome-based diagnostic and therapeutic strategies, aiming to provide new perspectives and theoretical foundations for precision medicine in prostate cancer.

2 Biological characteristics and isolation identification of exosomes

Exosomes are extracellular vesicles ranging from 30 to 150 nm in diameter. They are primarily composed of a lipid bilayer and contain a variety of biomolecules, including proteins, cellular metabolites, lipids, cytosolic components, ribonucleic acids, and nucleic acids (Figure 1A) (9). Exosomes can be secreted by nearly all cell types in the human body, such as stem cells, tumor cells, dendritic cells, macrophages, and other cell types (4). The specific origin of these exosomes can be determined by their surface ligands and receptors, playing key roles in intercellular communication and immune response modulation (10).

Figure 1

Figure 1. Exosome biogenesis, composition, and isolation/identification methods. (A) Exosomes originate through a conserved biogenic pathway initiated by donor cell plasma membrane internalization, forming early endosomes that progressively mature into late endosomes. During maturation, endosomal membranes undergo inward invagination to generate intraluminal vesicles (ILVs). These ILV-containing structures are designated multivesicular bodies (MVBs). Exosome release occurs upon MVB fusion with the plasma membrane, liberating ILVs into the extracellular space. (B) Common components of exosomes. DNA, RNA, four spanning proteins (CD9, CD63, CD81), PD-L1, integrin; Wnt proteins, ALIX, Syntenin, HSPs, GPC1, Rabs, Flotilin, etc. (C) Common isolation and identification methods of exosomes. Created with BioRender.com.

The body tightly regulates the biogenesis of exosomes. Exosomes are generated from the endosomal system (Figure 1B) (11). The formation of early endosomes (ILVs) is primarily due to the invagination of the cell membrane, leading to the formation of MVBs. During the transport of ILVs and the formation of MVBs, the endosomal sorting complex required for transport (ESCRT) plays a critical role (12). The ESCRT complex consists of ESCRT-0, ESCRT-I, ESCRT-II, ESCRT-III, and Vps4 (13, 14). ESCRT-0 is responsible for clustering ubiquitinated cargo proteins, while ESCRT-I/II assist in membrane curvature, ESCRT-III drives membrane scission, and Vps4 promotes the disassembly and recycling of the complex. Interestingly, several studies have shown that when ESCRT expression is inhibited, ILVs still form MVBs, suggesting that MVBs can also be generated through an ESCRT-independent pathway (15). Neutral sphingomyelinase 2 (nSMase2) generates ceramide, which promotes MVB invagination and ILV formation, and this pathway can be blocked by inhibitors like GW4869 to suppress exosome release (16). After MVB formation, they can either fuse with lysosomes or autophagosomes for degradation or merge with the plasma membrane via SNAREs and RabGTP proteins to release ILVs through exocytosis. Additionally, transmembrane proteins play a crucial role in this process. Numerous studies have indicated that transmembrane proteins such as CD9, CD69, CD81, CD82, CD61, heat shock proteins (HSP60, HSP70, and HSP90), tumor susceptibility gene 101 (TSG101), and integrins like ITGA3 and ITGB1 are involved in both ESCRT-dependent and -independent pathways of exosome biogenesis, thereby regulating cellular homeostasis (4, 17–20). However, the mechanisms and components of exosome biogenesis are modulated by different cell types (e.g., tumor cells, immune cells) and microenvironments (e.g., inflammation, hypoxia), displaying significant spatiotemporal and cell specificity, which warrants further investigation.

Exosomal cargo—encompassing proteins, lipids, and nucleic acids—mediates critical processes in cancer progression, immune regulation, and cardiovascular pathologies. These vesicles operate through two fundamental mechanisms: surface molecules directly activate intracellular signaling cascades upon binding target cell receptors, while membrane fusion enables cargo delivery to reprogram recipient cell function. Within tumor microenvironments, exosomes derived from tumor cells, immune cells (e.g., myeloid-derived suppressor cells [MDSCs]), and stromal cells critically influence disease dynamics by driving angiogenesis, enabling immune evasion, accelerating metastasis, and conferring drug resistance. Notably, such resistance manifests through chemoprotection or immunosuppression, thereby orchestrating tumor initiation, progression, and therapeutic responses (21). Crucially, beyond their pro-tumorigenic roles, exosomes also demonstrate significant potential as anti-cancer agents and therapeutic delivery platforms (22).

Exosomes are commonly found in various biological fluids, and their isolation and identification primarily rely on their physical properties—such as size and density—as well as specific immunological characteristics (Figure 1C) (23). Currently, widely used isolation techniques include differential ultracentrifugation, precipitation, immunoaffinity purification, size exclusion chromatography, and ultrafiltration (24). Differential ultracentrifugation is considered the “gold standard” and the most widely employed technique for exosome isolation, owing to its ability to process large sample volumes without the need for additional labeling, along with minimal contamination and relatively low operational cost. This method primarily includes density gradient centrifugation and differential centrifugation. However, it also has notable drawbacks, such as the requirement for expensive equipment, time-consuming procedures, and the potential to damage exosomal structure and integrity (25). Precipitation-based methods, in contrast, offer operational simplicity and high efficiency, and are suitable for a wide range of sample volumes, including both small and large-scale preparations. Despite these advantages, precipitation techniques suffer from significant limitations: they often co-precipitate non-specific contaminants, hinder accurate quantitative analysis of exosomal components, and are generally unsuitable for subsequent detailed characterization and functional studies of exosomes (26). Immunoaffinity purification-based purification leverages the specific binding between antibodies and antigens to isolate targeted exosome populations. While this approach allows for the selective capture of specific exosomes, it may also co-isolate non-specific vesicles and is generally unsuitable for large-scale sample processing (27). Size exclusion chromatography separates exosomes based on their hydrodynamic diameter, enabling high-purity isolation while preserving their structural integrity and biological activity. It is compatible with both small- and large-volume samples. However, the high cost of instrumentation and the inability to completely eliminate contaminants of similar size remain key limitations (28). Ultrafiltration utilizes membranes with defined pore sizes to concentrate and isolate exosomes, offering a cost-effective alternative to SEC. Nevertheless, membrane clogging can significantly reduce filter lifespan and affect reproducibility (29). Exosome identification typically relies on a combination of particle size, concentration, morphology, and surface markers (30). Commonly used characterization techniques include: Transmission electron microscopy (TEM) for assessing exosomal shape and size (31); Nanoparticle tracking analysis (NTA), which measures particle size and concentration based on light scattering and Brownian motion (32); Western blot, which quantifies exosomal protein markers (33); Flow cytometry, which enables quantitative analysis and surface marker-based sorting using fluorescent labeling (34); Additionally, PKH67 fluorescent labeling (35) and enzyme-linked immunosorbent assays (ELISA) (36) are also employed. Exosome isolation and identification strategies must align with experimental objectives and sample specifications. With ongoing technological advancements, exosome research continues to benefit from improvements in both isolation and identification methodologies, expanding their potential applications in biomedical science.

3 Exosomes in prostate cancer: promoting tumor progression

Acting as intercellular messengers, exosomes transfer biomaterials between cells. This process reprograms target cells, influencing their proliferation, survival, and immune surveillance. Released by virtually all cell types, including both benign and malignant prostate tissues, accumulating evidence indicates exosomes primarily exert detrimental effects in PCa (37). Here, we summarize the tumor-promoting effects of exosomes in PCa, including mechanisms such as EMT, angiogenesis, metastasis, tumor microenvironment formation, and the development of resistance to anticancer therapies (Figure 2).

Figure 2

Figure 2. Exosomes in prostate cancer: promoting tumor progression. Exosomes promote prostate cancer by promoting EMT, angiogenesis, tumor microenvironment formation, immune escape, and antitumor drug resistance. The parts indicated in the diagram are: (A) [Exosome-Mediated EMT], (B) [Exosome-Mediated Angiogenesis], (C) [Exosome-Mediated Cancer Metastasis], (D) [Exosome-Mediated TME Shaping], (E) [Exosome-Mediated Cancer Drug Resistance]. Created with BioRender.com.

3.1 Exosome-mediated epithelial–mesenchymal transition in prostate cancer

EMT is a process in which epithelial cells acquire mesenchymal characteristics during different cellular states, leading to reduced cell adhesion while gaining invasive and metastatic capabilities (38). Exosome-mediated EMT critically drives PCa progression.

Studies have found that the integrin α2 subunit (ITGA2) promotes cancer progression and metastasis. Exosomes derived from CRPC cells are enriched with ITGA2, which enhances focal adhesion kinase (FAK) and ERK1/2 activity in recipient cells, thereby promoting EMT. This process increases cell proliferation, migration, and invasion, ultimately driving the progression of PCa into a more aggressive form (39). Li et al. demonstrated that prostate-specific G protein-coupled receptor (PSGR)-bearing exosomes modulate bone metastasis-associated MAPK and NF-κB signaling through coordinated targeting of ICAM1, RELB, and IL1B, collectively driving EMT (40). Similarly, tumor-derived exosomes enriched with Cav-1 can induce neuroendocrine differentiation of PCa via the NF-κB signaling pathway, thereby promoting EMT (41). In addition, exosomes derived from PC3 cells carrying prostate-specific G protein-coupled receptors (PSGRs) promote EMT and stemness in low-invasive prostate cancer cells (LNCaP and RWPE-1), and also reshape the mRNA profile of LNCaP and RWPE-1 cells (42). Zhou et al. demonstrated in vivo and in vitro that serum exosomal miR-217 is significantly upregulated in PCa patients. This miRNA promotes tumor proliferation and invasion by modulating EMT markers—upregulating E-cadherin while downregulating vimentin (43). Josson et al. discovered that miR-409-3p/-5p in PCa exosomes can inhibit the expression of the tumor suppressor gene RAS suppressor 1 (RSU1), thereby promoting the EMT process (44). Exosome-derived circ-0081234 from cancer cells promotes EMT in PCa cells by inhibiting the expression of miR-1 and activating the MAP3K1 pathway (45). Wei et al. confirmed that exosomes carrying miR-423-5p in the bloodstream can target and inhibit FRMD3, thereby promoting EMT in PCa cells. This coordinated downregulation of E-cadherin with concomitant upregulation of N-cadherin and vimentin collectively promotes tumor proliferation, migration, and invasion in vivo (46). Under low androgen conditions, exosomes from cancer-associated fibroblasts (CAFs) isolated from PCa tissues exhibit a significant reduction in miR-146a-5p. This reduction further accelerates cancer cell metastasis by activating the EGFR/ERK axis through both in vitro and in vivo pathways, thereby enhancing EMT in PCa cells (47). These studies indicate that exosomes play a crucial role in mediating EMT and driving the progression of PCa.

3.2 Exosome-mediated angiogenesis

Angiogenesis generates new vascular networks to deliver oxygen and nutrients, enabling tumor growth and metastasis. Research shows that exosomes secreted by tumor cells constitute a primary angiogenesis-inducing mechanism.

In the context of various PCa hormone therapies, researchers have found complex interactions between androgen receptor (AR) signaling and exosome-mediated communication from PCa cells. These interactions enhance key factors in exosomes, such as AKT1, CALM1, PAK2, and CTNND1, which in turn stimulate tumor cell proliferation, migration, and angiogenesis (48). DeRita et al. demonstrated that PCa-derived exosomes carry elevated Src, insulin-like growth factor 1 receptor (IGF-IR), and FAK, driving angiogenesis (49). Under hypoxic conditions, prostate cancer-derived exosomes drive angiogenic processes by stimulating matrix metalloproteinase (MMP2/MMP9) activity and remodeling key extracellular matrix components (fibronectin, collagen), ultimately inducing vascular leakage that facilitates circulating tumor cell invasion (50). In addition, studies have shown that exosomal miR-27a-3p derived from PC-3 cells may participate in the angiogenesis process of CRPC (51). Liu et al. discovered that exosome-derived leucine-rich α2-glycoprotein 1 (LRG1) is involved in angiogenesis in PCa (52). Exosomal phosphoglycerate mutase 1 (PGAM1) promotes angiogenesis and invadopodia formation by interacting with ACTG1, thus initiating PCa cell metastasis and serving as a potential liquid biopsy marker for PCa metastasis (53).

Although angiogenesis plays a critical role in PCa, clinical studies of PCa have shown that anti-angiogenic therapies have failed to provide the expected clinical benefits and, instead, have increased toxicity, thereby promoting cancer progression (54). Current anti-angiogenic therapies for PCa demonstrate limited efficacy. The cited studies establish exosomes as pivotal mediators of PCa progression, particularly through neovascularization promotion, positioning them as promising therapeutic targets. Exosome-based strategies thus enable novel approaches for angiogenesis-targeted PCa treatment.

3.3 Exosome-mediated cancer metastasis

Approximately 90% of cancer-related deaths in humans are attributable to metastasis (55). Most malignant tumors are characterized by high invasiveness and a strong propensity for metastasis. The metastatic process involves a series of steps, including the invasion of primary tumor cells, survival within the circulatory system, and the subsequent adhesion to and colonization of distant organs (56, 57). Enhanced migratory capacity and immune evasion of cancer cells are key determinants driving these processes. Metastatic PCa commonly spreads to various organs, including bone, liver, lungs, and lymph nodes. Exosomes, as pivotal mediators of intercellular communication, play critical roles throughout multiple stages of tumor metastasis.

The skeleton is a common target organ for PCa metastasis. Tumor growth in bone arises from tumor-bone crosstalk that dysregulates physiological bone homeostasis. This balance, governed by osteoblast-mediated formation and osteoclast-driven resorption, establishes a pre-metastatic niche. Accumulating evidence confirms exosomal mediation of communication between PCa cells and the bone metastatic microenvironment. Yu et al. demonstrated that exosomal miRNA-92a-1-5p derived from PCa cells disrupts the balance between osteoblasts and osteoclasts by directly targeting and suppressing COL1A1, thereby promoting osteoclast differentiation while inhibiting osteoblastogenesis. This imbalance accelerates degradation and remodeling of the bone extracellular matrix (ECM) and facilitates the formation of a pre-metastatic niche, creating favorable conditions for PCa bone metastasis (58). Yang et al. further demonstrated that PC-3 cell-derived exosomes suppress osteoclast differentiation via miR-214 downregulation and NF-κB pathway blockade, enhancing PCa infiltration at bone metastatic sites (59). Concurrently, PCa exosomal miR-375 activates Wnt signaling by targeting DIP2C, driving osteoblastic metastasis (60). Additionally, exosomal miR-1275 upregulates RUNX2 (a key osteoblast regulator) through SIRT2 inhibition, promoting osteoblast proliferation and function to accelerate PCa bone metastasis (61). Interestingly, NEAT1 critically regulates osteogenic differentiation in PCa-associated human bone marrow-derived mesenchymal stem cells(hBMSCs). PCa-derived exosomal NEAT1 transfers to hBMSCs, where it competitively sequesters miR-205-5p and modulates the SFPQ/PTBP2 axis. This cascade upregulates RUNX2, inducing osteogenic differentiation (62). Through osteogenic assays (alkaline phosphatase activity, matrix mineralization, and osteogenic markers), Li et al. confirmed that LNCaP-derived exosomal miR-375 potently promotes osteoblastic activity (63). Additionally, exosomal miR-150-5p may facilitate PCa bone metastasis, primarily through inhibition of the Wnt signaling pathway, as suggested by Gene Ontology (GO) and KEGG pathway analyses (64). Multiple studies have also reported that exosomal miR-409 and miR-141 derived from PCa cells can target the small heterodimer partner (SHP), contributing to bone metastasis (65, 66). Collectively, these findings indicate that exosomes can disrupt the homeostatic balance between osteoblasts and osteoclasts, thereby influencing the metastatic progression of PCa.

Moreover, additional studies have demonstrated that exosomes play a pivotal role in mediating PCa metastasis. Ding et al. demonstrated in vivo and in vitro that exosomal circTFDP2 binds PARP1 at its DNA-binding domain, inhibiting caspase-3-dependent PARP1 cleavage. This suppression reduces DNA damage in PCa cells, ultimately promoting tumor proliferation and metastasis (67). Gao et al. identified S100A9-enriched exosomes from MDSCs as key regulators that upregulate circMID1 in PC3 cells through miR-506-3p sponging, thereby promoting tumor cell proliferation, invasion, and migration (68). Han et al. further demonstrated that engineered exosomes targeting SIRT6 effectively inhibit the metastatic potential of PCa cell lines (69). Additionally, silencing of exosomal carbonic anhydrase I (CA1) in PC3 cells enhances tumor cell migration and invasion (70). Dai et al. found that exosomal miR-183 from PCa cells promotes cancer cell invasion and migration by downregulating TPM1 expression (71). Under hypoxic conditions, cancer-associated fibroblast (CAF)-derived exosomal miR-500a-3p, isolated from PCa tissues, promotes PCa metastasis by suppressing FBXW7 expression and upregulating HSF1, suggesting that miR-500a-3p may serve as a promising therapeutic target for metastatic PCa (72). Comparative RNA-seq of CAF- versus normal fibroblasts-derived exosomes from PCa/adjacent tissues identified differentially expressed miRNAs. Specifically, CAF-exosomal miR-1290 promotes PCa progression by suppressing GSK3β/β-catenin signaling, highlighting its therapeutic potential (73). Separately, Fabbri et al. showed that exosomal miR-21/29a activate TLR7/8 in immune cells, triggering pro-metastatic inflammation that facilitates tumor dissemination (74).

Collectively, accumulating evidence reveals exosomes as pivotal mediators of PCa metastasis through multifaceted molecular pathways. Vesicular cargo—particularly circRNAs, miRNAs, and proteins—orchestrate signaling cascades that drive malignant behaviors (proliferation, invasion, migration) while simultaneously remodeling tumor microenvironments and pre-metastatic niches. These insights fundamentally advance our comprehension of exosome-driven intercellular communication in PCa progression, extending beyond mechanistic understanding to reveal promising diagnostic biomarkers and therapeutic targets against metastatic disease.

3.4 Exosome-mediated tumor microenvironment remodeling and immune evasion in prostate cancer

The TME encompasses the dynamic cellular and molecular milieu surrounding neoplastic tissue. It is primarily composed of neighboring blood vessels, stromal cells (e.g., fibroblasts and neuroendocrine cells), immune cells (e.g., T lymphocytes, natural killer (NK) cells, dendritic cells (DCs), and macrophages), adipose-derived stem cells, various signaling molecules, and the extracellular matrix (ECM). It represents a complex and continuously evolving biological process. This evolving biological ecosystem facilitates complex intercellular communication in PCa through ECM remodeling, metabolic reprogramming, immune suppression, and angiogenesis. Based on the TME features that facilitate tumor initiation, survival, and metastasis, three major subtypes are recognized: hypoxia, inflammation, and immune suppression. Exosomes orchestrate these processes by establishing multifaceted communication networks. During TME reprogramming, exosomes serve as critical vectors for long-distance transport of bioactive cargo. In advanced malignancies, bidirectional crosstalk between the TME and tumor-derived exosomes drives proliferation, confers therapy resistance, and enables metastatic dissemination (75). As master regulators of intercellular signaling, exosomes play pivotal roles in PCa TME development.

Under hypoxic conditions, exosomes derived from LNCaP and PC3 prostate cancer cells modulate adherens junction protein expression. This remodeling enhances tumor cell aggressiveness and stemness while inducing microenvironmental alterations, collectively driving PCa progression (76). Abd Elmageed et al. demonstrated that the PCa microenvironment induces tumorigenic transformation of patient-derived adipose-derived stem cells (ADSCs). Mechanistically, this neoplastic reprogramming is mediated by PCa cell-secreted exosomes carrying specific microRNAs (miR-125b, miR-130b, and miR-155). These findings provide novel mechanistic insights into molecular drivers of PCa progression (77). Upregulated hyaluronidase 1 (Hyal1) in prostate tumor cells accelerates vesicular trafficking to potentiate stromal cell migration. Mechanistically, exosome-transferred Hyal1 executes its pro-tumorigenic functions by augmenting cellular adhesion to type IV collagen substrates, facilitating dynamic membrane clustering of β1 integrins, and propagating FAK phosphorylation. This concerted mechanism drives Hyal1-dependent PCa progression through extracellular matrix remodeling and motility activation (78).

Neuroendocrine cells drive disease progression through autocrine/paracrine secretion of peptide hormones and growth factors. Hormone-treated prostate cancers frequently develop neuroendocrine differentiation (NED), a phenotype associated with therapeutic resistance and poor survival. Exosomes derived from PC3 cells—with or without growth hormone-releasing hormone (GHRH) preconditioning—induce NED in LNCaP cells, evidenced by increased neurite-bearing cell populations, elevated neuron-specific enolase (NSE) expression, and enhanced proliferative/adhesive capacities. Notably, exosomes from GHRH-primed PC3 cells accelerate LNCaP proliferation more rapidly than those from untreated controls (79). Under IL-6 stimulation or androgen-deprived conditions, exosomal adipocyte differentiation-related protein (ADRP) from DU145 and LNCaP prostate cancer cells induces NED in CRPC through paracrine activation of peroxisome proliferator-activated receptor γ (PPARγ), a master adipogenic transcription factor (80). Notably, Bhagirath et al. demonstrated that exosomes from enzalutamide-resistant PCa models (LNCaP, Du145, PC3, C42B, NCI-H660) drive oncogenic lineage plasticity toward neuroendocrine states via release of neural transcription factors BRN2 and BRN4 (81).

The TME harbors abundant yet functionally impaired immune cells that facilitate tumor immune evasion. Mounting evidence indicates tumor-derived exosomes mediate immunosuppressive reprogramming of immune cells to establish a pro-tumorigenic niche in PCa. CD8⁺ T-cell depletion constitutes a major barrier to immunotherapy efficacy. Specifically, LNCaP-derived exosomes enriched with Fas ligand (FasL) induce apoptosis in CD8⁺ T lymphocytes (82). Xu et al. further revealed that PCa-derived exosomes shuttle IL-8 to suppress CD8⁺ T-cell function. Mechanistically, exosomal IL-8 hyperactivates PPARα in recipient cells, impairing glucose utilization through GLUT1/HK2 downregulation. This PPARα activation upregulates UCP1, redirecting fatty acid catabolism from ATP synthesis toward thermogenesis. This metabolic rewiring induces CD8⁺ T-cell bioenergetic crisis and functional exhaustion, facilitating immune escape (83). Parallel immune evasion occurs through NKG2D receptor modulation. As a critical cytotoxic receptor expressed on NK and CD8⁺ T cells, NKG2D plays pivotal roles in antitumor immunity. Mali et al. revealed that exosomal NKG2D ligands on human PCa cells selectively downregulate NKG2D expression in a dose-dependent manner. This ligand-mediated cis-regulation compromises cytolytic function of both NK and CD8⁺ T cells, promoting immunosuppression and tumor evasion (84). Salimu et al. further revealed that PCa -derived exosomes impair dendritic cell (DC) capacity for tumor antigen cross-presentation. Building on prior observations of these exosomes suppressing IL-2 secretion in CD4⁺ T cells and inducing ecto-5’-nucleotidase (CD73) surface expression on DCs, mechanistic studies identified exosome-borne prostaglandin E2 (PGE2) as the principal mediator of CD73 upregulation. This PGE2-CD73 axis critically disrupts DC functionality, providing novel insights into exosome-facilitated immune evasion through DC reprogramming (85). Cellular studies by Han et al. revealed that RNF157 mRNA within prostate cancer-derived exosomes is transported to macrophages, where its translation product binds histone deacetylase 1 (HDAC1). This interaction promotes HDAC1 ubiquitination, triggering ubiquitin-proteasomal degradation. The resultant HDAC1 depletion culminates in macrophage repolarization toward an M2-like phenotype. In vivo validation established that exosomal RNF157 accelerates prostate tumor growth through TAM-mediated M2 polarization in xenograft models (86). Under endoplasmic reticulum (ER) stress, prostate cancer cell-derived exosomes drive macrophage polarization toward an M2-like phenotype. This reprogramming involves exosomal transmission of stress signals that activate the PI3K/Akt pathway in macrophages. Akt-mediated signaling upregulates M2-associated genes (e.g., CD206, PD-L1) while suppressing CD16 (FcγRIII) expression, resulting in immunosuppressive functional conversion. These polarized tumor-associated macrophages (TAMs) secrete immunosuppressive factors that blunt antitumor immunity, facilitating tumor immune evasion, invasion and metastasis of tumor cells (87). Concurrently, PCa exosomes modulate MDSCs—key immunosuppressive populations that dampen immune effector responses. Li et al. demonstrated that tumor exosomes activate TLR2/NF-κB signaling in MDSCs, markedly upregulating surface CXCR4 expression. Enhanced CXCR4 levels potentiate MDSC chemotaxis toward CXCL12 gradients in the TME via CXCR4-CXCL12 axis-driven migration. Critically, pharmacological TLR2 inhibition using C29 antagonist significantly attenuated CXCR4 expression and impaired MDSC trafficking, confirming TLR2/NF-κB’s pivotal role in myeloid cell recruitment (88). Research indicates that CAFs, derived from fibroblasts and mesenchymal stem cells, promote tumor growth (89). Transforming growth factor-β (TGF-β) plays a critical role in the generation and maintenance of CAFs (90). For instance, exosomes derived from PCa cell lines (LNCaP, DU145, and PC3) exhibit surface enrichment of TGF-β. This TGF-β can activate SMAD3-associated signaling pathways, thereby inducing the acquisition of a CAF phenotype (91).

Furthermore, studies by Cui et al. demonstrate that exosomes originating from CAFs deliver glucosamine to PCa cells. Within the recipient cancer cells, this glucosamine elevates the levels of O-linked β-N-acetylglucosamine modification (O-GlcNAcylation) (92). O-GlcNAcylation, a crucial post-translational modification involving the attachment of β-N-acetylglucosamine to serine/threonine residues, modulates cellular nutrient sensing and stress responses. This modification subsequently enhances the transcriptional activity of the transcription factor ELK1. Activated ELK1 upregulates the expression of HSD3B1, the rate-limiting enzyme in steroid synthesis (93). The increased HSD3B1 expression stimulates de novo androgen synthesis within the tumor cells, activating the androgen receptor (AR) signaling pathway. Ultimately, this cascade drives the progression of CRPC (93). Wang et al. demonstrated a significant elevation in miR-1290 levels within exosomes derived from CAFs in PCa tissue. These CAF-secreted exosomes deliver miR-1290 to PCa cells, enhancing their migratory and invasive capacities and inducing EMT. Mechanistic investigations revealed that exosomal miR-1290 targets glycogen synthase kinase 3β (GSK3β), downregulating its expression and consequently impairing the GSK3β/β-catenin signaling axis. Specifically, the suppression of GSK3β expression diminishes β-catenin degradation, leading to its accumulation in the cytoplasm and nucleus. This accumulated β-catenin activates the transcription of downstream pro-metastatic genes, ultimately promoting an aggressive tumor phenotype (73).

In summary, exosomes critically orchestrate the PCa tumor microenvironment and enable immune evasion. Deciphering their molecular mechanisms in mediating tumor-immune cell crosstalk—particularly with key immune populations (NK cells, T cells, tumor-associated macrophages (TAMs), MDSCs, dendritic cells (DCs))—is essential. This knowledge will establish a theoretical foundation for developing exosome-targeted immunotherapies and guide the design of precise therapeutic interventions.

3.5 Exosome-mediated resistance to anticancer therapies

Drug resistance development poses a major challenge in cancer therapy. Exosomes, as critical mediators of intercellular communication, play essential roles in conferring tumor drug resistance (94). Nanoparticle tracking analysis has shown that docetaxel (DTX)-resistant DU145 PCa cells release a significantly higher quantity of exosomes compared to their DTX-sensitive counterparts (95). Clinical studies evaluating the protein content of exosomes derived from PCa patients have confirmed that PCa cell-derived exosomes markedly regulate tumor cell invasiveness and chemoresistance. Cumulative evidence suggests that exosome-mediated drug resistance in tumors is governed by a variety of complex molecular mechanisms. These include: (1) the direct expulsion of chemotherapeutic agents via exosomal secretion, (2) the transfer of resistance-associated cargos from resistant to drug-sensitive tumor cells through exosomal communication, and (3) the role of exosomes as decoys in immune-based therapies (94, 96). Among these, numerous studies have primarily attributed tumor drug resistance to the second mechanism, whereby exosomal transfer of molecular contents contributes to the dissemination of resistance traits.

Multiple studies have indicated that specific exosomal microRNAs play pivotal roles in mediating chemoresistance in cancer cells. For example, Corcoran et al. identified four miRNAs—miR-598, miR-34a, miR-146a, and miR-148a associated with DTX resistance in PCa using RNA expression microarray analysis. Among them, miR-34a primarily contributes to DTX resistance by inhibiting the expression of BCL-2 (97). Similarly, Li et al. reported that exosomal miRNAs, including miR-32-5p, miR-141-3p, miR-606, miR-381, and miR-429, may induce chemoresistance in PCa by modulating the androgen receptor, PTEN, and the hub gene TCF4 (T-cell factor/lymphoid enhancer-binding factor 4) (98). One study demonstrated that exosomes secreted by primary PCa fibroblasts are enriched in miR-27a, which suppresses p53 expression in PC3 cells, thereby exacerbating chemoresistance in metastatic castration-resistant PCa (mCRPC) cells (99). Additionally, exosomal miR-432-5p derived from CAFs isolated from patient-derived PCa tissues was shown to promote DTX resistance by targeting CHAC1, reducing glutathione (GSH) consumption, and ultimately inhibiting ferroptosis in PCa cells (100). Moreover, miR-423-5p in CAF-derived exosomes confers taxane resistance in PCa by suppressing TGF-β signaling and downregulating GREM2 (101).

Similarly, other exosomal components have also been implicated in mediating drug resistance in PCa. The acquisition of DTX resistance in DTX-sensitive PCa cell lines (DU145, 22Rv1, and LNCaP) has been associated with the exosomal release of multidrug resistance protein 1/P-glycoprotein (MDR-1/P-gp) (102). In another study, silencing P-gp expression in exosomes significantly reduced DTX resistance in PC3 cells, suggesting that exosomal P-gp plays a critical role in mediating chemoresistance in PCa (103).Additionally, circSLC4A7, enriched in exosomes derived from resistant PCa cells, was found to promote DTX resistance via the miR-1205/MAPT axis (104). The exosomal circular RNA circ-XIAP (X-linked inhibitor of apoptosis) directly targets and inhibits miR-1182, thereby upregulating TPD52 expression and contributing to DTX resistance in PCa, which may represent a promising therapeutic target for overcoming chemoresistance (105). Tan et al. further demonstrated that exosomal circ-SFMBT2, which contains four malignant brain tumor domains, enhances DTX resistance in PCa by suppressing miR-136-5p and upregulating TRIB1 expression (106). Moreover, exosomes derived from LNCaP cells are enriched in Caveolin-1, which can confer DTX chemoresistance to recipient cells and increase their survival following radiotherapy (41). Bhagirath et al. revealed that resistance to enzalutamide and the induction of treatment-associated NED in PCa are also mediated via exosomes (81). Notably, inhibiting exosome secretion partially restored enzalutamide sensitivity in resistant PCa cells. Furthermore, enzalutamide-treated PCa cells release exosomes carrying the neuronal transcription factors BRN2 and BRN4, which drive oncogenic reprogramming of prostate adenocarcinoma toward a neuroendocrine phenotype (81).

LincROR is upregulated in doxorubicin-resistant PCa cells and undergoes hnRNPA1-dependent exosomal packaging. This facilitates chemoresistance transfer to recipient cells, promoting DTX resistance in PCa. Mechanistically, lincROR stabilizes MYH9 protein via direct interaction, activating β-catenin/hypoxia-inducible factor 1-alpha (HIF1α) signaling. These findings indicate that exosomal lincROR drives DTX resistance through a β-catenin/HIF1α positive feedback loop (107). Separately, Zhang et al. reported that CAF-secreted neuregulin 1 (NRG1) activates HER3 in tumor cells, enhancing androgen deprivation therapy resistance. Pharmacological inhibition of the NRG1-HER3 axis effectively suppresses hormone resistance development (108).

Collectively, these studies highlight exosomes as key mediators of PCa drug resistance, positioning exosome-targeting strategies as promising therapeutic approaches to overcome chemoresistance.

4 Exosomes in prostate cancer: tumor-suppressive roles

Beyond the documented detrimental roles of exosomes in PCa progression, emerging evidence supports their tumor-suppressive functions (Figure 3).

Figure 3

Figure 3. Exosomes in prostate cancer: tumor-suppressive roles. The pale red section on the left indicates exosomal components derived from prostate cancer cells, while the paleyellow section on the right represents exosomal materials from bone marrow-derived mesenchymal stem cells (BMSCs) and fibroblasts. Created with BioRender.com.

Exosomal hsa-miR-184 derived from the plasma of PCa patients acts as a novel negative regulator of angiogenesis by targeting Argonaute 2 (AGO2), a core component of the RNA-induced silencing complex (RISC), in human umbilical vein endothelial cells (HUVECs). Mechanistic studies demonstrate that exosome-delivered high levels of hsa-miR-184 significantly suppress AGO2 expression. This suppression consequently impairs HUVEC proliferation, migration, and in vitro tube formation capacity, ultimately blocking tumor-associated angiogenesis. This finding establishes exosomal hsa-miR-184 as a novel anti-angiogenic factor in PCa and highlights its translational potential as a therapeutic target for anti-angiogenic strategies (109). Exosomal miR-26a originating from the low-grade PCa cell line LNCaP significantly modulates the expression of EMT-related factors. This includes downregulating matrix metalloproteinases (MMP-2, MMP-9) and mesenchymal markers (N-cadherin, Vimentin), while concurrently upregulating the tissue inhibitor of metalloproteinase 2 (TIMP2) and the epithelial marker E-cadherin. This inhibitory effect on the EMT process ultimately results in a significant attenuation of PCa cell metastatic potential and in vivo tumor growth (110).Tian et al. reported that exosomes derived from PC-3 cells suppress osteoclast differentiation via downregulation of miR-148a. This suppression was manifested by reduced expression of osteoclast maturation markers integrin β3 (ITGβ3) and matrix metalloproteinase 9 (MMP-9), alongside upregulated expression of the transcription factor MAFB. This process effectively prevents PCa bone metastasis through blockade of the PI3K/AKT/mTOR signaling pathway (111). Increased circHIPK3 levels in serum exosomes of PCa patients drive oncogenesis. Functional studies show that circHIPK3 knockdown inhibits tumor growth and metastasis through miR-212/BMI-1 signaling (112). Zhou et al. identified a significant decrease in the expression of exosomal miR-23b-3p in the serum of PCa patients. Functional investigations revealed that restoring miR-23b-3p expression effectively suppressed PCa cell proliferation and invasion. Mechanistically, miR-23b-3p modulates the expression profile of EMT-related proteins by targeting specific signaling pathways. This involves upregulating the epithelial marker E-cadherin while downregulating mesenchymal markers N-cadherin and Vimentin, thereby reversing the pro-metastatic EMT phenotype (43). Research by Honeywell et al. demonstrated that exosomal miR-105 derived from prostate tumor cell lines (PC3 and DU145) potently inhibits the proliferative activity of PCa cells by specifically targeting and suppressing the expression of cyclin-dependent kinase 6 (CDK6) (113). A1BG-AS1 is a lncRNA whose stability is enhanced via ZC3H13-mediated m⁶A modification. Studies indicate that exosomal delivery and m⁶A RNA modification play crucial regulatory roles in PCa progression (53, 114–116). ZC3H13 promotes the stable expression of A1BG-AS1 by regulating its m⁶A levels. Exosomes derived from PCa cells are enriched in m⁶A-modified A1BG-AS1, which suppresses tumor progression through a ZC3H13-dependent mechanism (117). Guo et al. reported that exosomes secreted by heat-stressed tumor cells (HS-TEXs), enriched in heat shock protein 70 (HSP70), inhibit tumor growth. This occurs by triggering IL-6-mediated immunomodulation that promotes the conversion of regulatory T cells (Tregs) to T helper 17 (Th17) cells (118). Engineered nanocarriers based on cancer cell-derived exosomes have achieved tumor-specific targeted delivery. For instance, the Exo-PMA/Fe-HSA@DOX nanosystem utilizes urine exosome-mediated homologous targeting. It concurrently blocks the epidermal growth factor receptor (EGFR) and its downstream AKT/NF-κB/IκB signaling pathway, synergizing chemotherapy with photothermal therapy (chemo-PTT) to induce cancer cell apoptosis (119). Notably, a study exploring racial disparities in PCa revealed that exosome secretion was markedly increased under hypoxic conditions across multiple human PCa cell lines (including LNCaP, 22Rv1, PC-3, and PWR-1E). This adaptive response may confer a survival advantage by eliminating metabolic waste products like lactate, thereby maintaining intracellular metabolic homeostasis within tumor cells. This mechanism was particularly pronounced in African American patients, suggesting that exosome-mediated metabolic reprogramming exhibits racial specificity in PCa progression (120).

Mesenchymal stem cell (MSC)-derived exosome therapy represents a novel strategy for targeted PCa treatment. It demonstrates significant potential in modulating the tumor microenvironment and delivering functional molecules, providing a new direction for developing highly efficient and precise therapeutic regimens (121). Exosomes originating from MSCs effectively inhibit PCa progression through multi-pathway regulation. Key mechanisms include: (1) upregulating the epithelial marker E-cadherin while downregulating the EMT transcription factor Snail to reverse EMT; (2) suppressing the expression of pro-angiogenic factors VEGF-A and VEGF-C to block tumor angiogenesis; and (3) modulating the balance between pro-apoptotic genes (BAX, p53) and anti-apoptotic genes (BCL2), thereby inducing cancer cell apoptosis (122). Exosomal miR-187 delivered by bone marrow MSC-derived exosomes (BMSC-exos) directly targets the immune checkpoint molecule CD276. This interaction inhibits the activation of the JAK3-STAT3 signaling axis and its downstream transcription factor Slug, consequently blocking aggressive PCa phenotypes (123). Human bone marrow MSC (hBMSC)-derived exosomal miR-99b-5p directly targets and suppresses insulin-like growth factor 1 receptor (IGF1R) expression, thereby impeding malignant PCa progression (124). Exosomal miR-205 sourced from hBMSCs significantly delays PCa progression by targeting and inhibiting the expression of Ras homolog protein RHPN2. This mechanism suggests miR-205 holds dual value as both a potential disease biomarker and a therapeutic target (125). Exosomes secreted by human MSCs pre-labeled with superparamagnetic iron oxide nanoparticles (Venofer^®) – a process that did not significantly alter cellular proliferation or tumor-homing capacity – are efficiently internalized by tumor cells. These labeled exosomes suppress tumor growth in a dose-dependent manner and, under exogenous alternating magnetic field-induced hyperthermia, significantly potentiate tumor cell ablation (126).

Placental stem cell-derived exosomes exhibit selective growth inhibitory effects on highly aggressive PCa cells, with their specific targeting mechanism potentially involving tumor microenvironment modulation (127). Fibroblast-derived exosomal miR-3121-3p maintains the differentiated state in androgen-sensitive PCa cells by targeting and promoting the expression of the tumor suppressor gene NKX3-1, thereby antagonizing oncogenic dedifferentiation (128).

Collectively, these studies establish exosomes as master regulators of PCa advancement. Through targeted delivery of functional non-coding RNAs (e.g., miR-26a, miR-184, circHIPK3), they orchestrate EMT, angiogenesis, immune modulation, and metabolic reprogramming. Their inhibitory actions—such as blocking CD276/STAT3 signaling, AGO2 function, and PI3K/AKT pathways—robustly suppress tumor proliferation, metastasis, and therapy resistance. These insights unveil promising avenues for developing exosome-based diagnostic biomarkers, engineered nanotherapies, and immunocellular treatments.

5 Exosome-based diagnostic and therapeutic strategies for prostate cancer: current advances and clinical prospects

5.1 Exosomes as potential diagnostic and prognostic biomarkers for prostate cancer

Previous studies have confirmed that exosomes serve as biomarkers for cancer pathogenesis due to their distinctive biological properties (129–131). In PCa diagnostics and management, exosomes demonstrate significant utility not only as potential biomarkers but also for multiple clinical contexts including disease staging, early detection, progression monitoring, prognostic evaluation, and therapeutic response tracking. Their ubiquitous presence in diverse biofluids—such as plasma, urine, and semen (Table 1)—establishes exosomes as a valuable reservoir for PC liquid biopsies. This section systematically reviews advances in exosome-based diagnostic and predictive indicators for PC.

Table 1

Table 1. Exosomes as diagnostic biomarkers for PCa.

A prospective cohort study (n=62) conducted by West China Hospital of Sichuan University on mCRPC revealed significantly elevated levels of exosomal AKR1C3 in patient plasma. Critically, survival analysis confirmed that exosomal AKR1C3 positivity serves as a significant predictor of reduced overall survival and progression-free survival. Consequently, plasma exosomal AKR1C3 detection holds promise as a novel prognostic biomarker for mCRPC patients (132). In parallel research, serum exosomes from PCa patients (n=39) exhibited marked overexpression of membrane proteins PSMA and caveolin-1 compared to those with benign prostatic hyperplasia (BPH) (n=33). This finding suggests that circulating exosomal PSMA and caveolin-1 quantification may enable early PCa diagnosis and prognostic assessment (133). Furthermore, a study of 34 PCa patients demonstrated substantially higher expression of lncRNAs SAP30L-AS1 and SChLAP1 in plasma exosomes versus controls. ROC analysis established that both lncRNAs individually distinguish PCa from BPH with high efficacy, while combining them with PSA further enhanced diagnostic accuracy (134). Collectively, SChLAP1 and SAP30L-AS1 represent promising diagnostic biomarkers, with their overexpression potentially correlating with tumor aggressiveness and disease progression.

In a screening cohort of 31 PCa patients, plasma exosomal RNA analysis via qRT-PCR identified miR-125a-5p and miR-141-5p as potential prognostic biomarkers (135). Concurrently, a multimodal approach combining qRT-PCR detection of downregulated serum exosomal miRNAs (miR-15a, miR-16, miR-19a-3p, miR-21) with ¹H-NMR metabolomic profiling successfully distinguished mCRPC patients from benign prostatic hyperplasia (BPH) cases (136). Further supporting prognostic utility, Huang et al. performed plasma exosomal RNA sequencing in 23 CRPC patients, validating that elevated miR-1290 and miR-375 levels significantly correlated with reduced overall survival (137). Diagnostically, Zhang’s team established a serum exosome-based 3-miRNA signature (miR-146a-5p, miR-24-3p, miR-93-5p) for PCa detection (138). Regarding therapeutic resistance, plasma exosomal AR-V7 measured by ddPCR in 36 CRPC patients predicted hormonal therapy resistance (139), while serum exosomal CD44v8–10 mRNA overexpression in 50 docetaxel-resistant CRPC cases demonstrated diagnostic value for chemoresistance (140). Notably, Li et al. revealed significantly elevated serum exosomal EphA2 receptor levels in 50 PCa patients versus BPH/controls. Exosomal EphA2 outperformed total serum EphA2 in discriminating PCa from BPH, indicating its dual role as the primary functional circulating EphA2 fraction and a dynamic biomarker for disease monitoring (141).

qRT-PCR profiling of serum exosomal miRNAs revealed miR-423-3p as the most significantly dysregulated species across multiple validation phases: an initial cohort (108 treatment-naïve PCa vs. 42 CRPC patients), an independent replication cohort (30 treatment-naïve vs. 30 CRPC), and 36 non-CRPC controls. Its expression consistently demonstrated robust correlation with CRPC status, supporting its potential as an early predictive biomarker (142). Concurrently, Lu et al. identified blood exosomal hsa-miR-125a-3p, -330-3p, -339-5p, and -613 as bone metastasis-specific signatures through integrated analysis of 10 metastatic PCa samples and the GSE26964 public dataset (143). Furthermore, exosomal αvβ3 integrin facilitates dynamic disease progression monitoring (144), while combined assessment of miR-1290, miR-375 (137), and AR-V7 (145) enables prognostic stratification in CRPC. For therapeutic response, exosomal miR-654-3p and miR-379-5p show promise in evaluating carbon ion radiotherapy (CIRT) efficacy (146).Critically, multi-analyte panels enhance diagnostic precision: the PCA3/PCGEM1 combination improves high-grade tumor detection, whereas TM256/LAMTOR1 co-assessment increases diagnostic sensitivity. Collectively, these advances establish a translational framework for blood exosomal biomarker implementation in clinical practice (147).

Beyond blood-derived exosomes, urinary and seminal exosomes demonstrate significant diagnostic and prognostic value in PCa. In post-DRE urine samples from 14 men with elevated PSA, exosomal miR-30b-3p and miR-126-3p exhibited superior sensitivity/specificity (46.4%/88.0% and 60.7%/80.0%, respectively) for PCa detection compared to serum PSA (53.5%/64.0%), highlighting their non-invasive diagnostic utility (148). Further investigations of urine-based AMACR—a tissue-overexpressed biomarker—revealed that while early AMACR protein assays showed limited specificity (100% sensitivity/58% specificity, n=26) (149), exosomal AMACR demonstrated enhanced performance (AUC = 0.832 for PCa vs. BPH; AUC = 0.78 for clinically significant PCa), outperforming PSA, f/t PSA, and PSAD (150). Additionally, urinary exosomal mRNA analyses confirmed significant overexpression of ERG, PSMA, and CK19 in PCa patients (151), while exosomal miR-21, miR-451, miR-636 (152), and miR-2909 (153) showed predictive value for metastasis. Moreover, additional studies have identified significant quantitative differences in urinary exosome content between PCa patients versus those with benign prostatic hyperplasia (BPH) or healthy individuals. These differential expression patterns involve multiple molecular species including miR-574-3p, miR-141-5p, miR-21-5p (154), miR-375 (155), miR-196a-5p, miR-501-3p (156), lncRNA-p21 (157), ITGA3 and ITGB1 (158), as well as lipid components such as phosphatidylserine and lactosylceramide (159). These collective findings establish the substantial diagnostic and prognostic significance of urine-derived exosomes in PCa. Collectively, these findings substantiate the substantial diagnostic and prognostic value of urine-derived exosomes in PCa management. Notably, a seminal exosome-based panel combining PSA with miR-142-3p, miR-142-5p, and miR-223-3p further improved PCa diagnostic and prognostic accuracy (160). Collectively, these findings underscore the translational promise of multi-source exosomal biomarkers in precision PCa management.

5.2 Exosome-based therapeutic strategies for prostate cancer: clinical translation prospects

Conventional chemotherapy for cancer treatment faces significant limitations. These include suboptimal bioavailability, poor tumor targeting, induction of chemoresistance and radioresistance, potential immune-related adverse effects, and insufficient drug specificity (172). These drawbacks underscore the urgent need for novel therapeutic approaches. Exosomes present a highly promising therapeutic platform for PCa, leveraging their innate capacity to transport bioactive cargo, ease of engineering for targeted delivery, high biocompatibility, and low immunogenicity. This review summarizes three key exosome-based therapeutic strategies: (1) Engineered exosomes as drug delivery vehicles, (2) Exosome-based targeting therapies, and (3) Exosome-mediated cellular immunotherapy (Figure 4).

Figure 4

Figure 4. Exosome-based therapeutic strategies: (A) Engineered exosomes as drug delivery vehicles, (B) Exosome-based targeting therapies, and (C) Exosome-mediated cellular immunotherapy. Created with BioRender.com.

As natural nanoscale bilayer vesicles, exosomes provide an ideal platform for precision-targeted therapy by leveraging their inherent immune privilege to evade host immune clearance while utilizing their bilayer architecture for site-specific delivery of diverse therapeutic payloads—including chemotherapeutics, nucleic acids, and natural compounds (173). Their targeting efficacy is augmented through dual mechanisms: engineered surface modifications optimize ligand presentation, and intrinsic biological barrier penetration promotes lesion-specific accumulation (174–177). Biomimetic exosomal nanoplatforms effectively replicate tumor-derived exosome functions, exemplified by Vázquez-Ríos et al. drug-loaded system demonstrating high targeting precision (178). In PCa models, autologous exosomes encapsulating paclitaxel selectively enhanced cytotoxicity against LNCaP and PC-3 cells (179), while anti-PSMA peptide-functionalized exosome-mimetics showed superior targeting toward PSMA-positive lineages (LNCaP, C4-2B) versus unmodified controls in vitro and in vivo (180). Exosome-mediated delivery of tumor suppressor miR-143 significantly inhibited PC-3M-luc proliferation (181), MSC-derived exosomes transporting miR-let-7c suppressed migration and proliferation in CRPC (182), and engineered exosomes delivering SIRT6 siRNA silenced this oncogenic factor to curb metastasis (69). Immunotherapeutically, interferon-γ-anchored exosome vaccines developed by Shi et al. activated immune-mediated clearance of tumor-derived exosomes, markedly inhibiting murine tumor progression and extending survival (183). A breakthrough composite carrier—CEXO@ZIF-8/DOX, integrating zeolitic imidazolate framework-8 (ZIF-8)-encapsulated doxorubicin core with cucurbit-derived exosome-mimetic nanoparticle (CEXO) shell—achieved precise targeting, selectively inducing cell cycle arrest and apoptosis in PC-3 cells while significantly suppressing tumor growth with manageable systemic toxicity, thereby establishing an innovative exosomal delivery paradigm (184). Collectively, exosomes emerge as a transformative delivery platform for chemotherapeutics, therapeutic nucleic acids, and natural products, capitalizing on engineerable targeting, exceptional biocompatibility, and versatile cargo-loading capabilities.

Exosomal components demonstrate significant therapeutic targeting potential in PCa. Ishizuya et al. identified substantial enrichment of actin-4 (ACTN4) in serum exosomes from CRPC patients through proteomic analysis. Subsequent RNAi-mediated ACTN4 knockdown effectively suppressed DU145 cell proliferation and invasion, establishing exosomal ACTN4 as a novel therapeutic target for CRPC (185). Similarly, Gan et al. documented upregulated miR-375 expression in prostate cancer-derived exosomes, revealing its targeting as a promising strategy for CRPC with high androgen receptor expression (186). Clinical translational studies demonstrate that exosomal AR-V7 detection shows positivity in 39% of CRPC patients, with AR-V7-negative cases exhibiting significantly prolonged progression-free survival, indicating exosomal AR-V7 targeting as a viable therapeutic approach (139). Mechanistically, under androgen deprivation or IL-6 stimulation, exosomes derived from DU145 and LNCaP cells induce NED via the PPARγ/ADRP pathway. Elucidating the role of adipocyte differentiation-related protein (ADRP) in this process offers innovative therapeutic targets for advanced CRPC (80). Collectively, these findings establish exosomes and their cargos as pivotal targets for precision therapy in PCa.

Exosome-mediated cellular immunotherapy represents an innovative direction for PCa treatment. Research demonstrates that prostate cancer-derived exosomes suppress antitumor immunity through three immunomodulatory pathways: Lu et al. revealed that tumor exosomes upregulate the inhibitory receptor NKG2A on NK cells, significantly impairing NK cell activity (NKA). Conversely, radical prostatectomy increased exosomal NKG2D ligands while downregulating NKG2A, thereby restoring NKA—suggesting that targeting the exosome-NKG2A axis can reactivate NK cell cytotoxicity (187). Parallel studies by Peng et al. confirmed that inhibiting exosome biogenesis with GW4869 blocks M2-polarization of tumor-associated macrophages, reversing immunosuppressive microenvironments (188). Complementary work by Liu et al. showed that the P300/CBP inhibitor A485 suppresses exosomal PD-L1 secretion by inhibiting CD274 transcription, subsequently enhancing CD8⁺ T cell infiltration to convert immunologically cold tumors into hot tumors and potentiate immune checkpoint therapy (189). Exosomes derived from heat-stressed tumor cells are enriched with HSP70. By inducing IL-6-mediated immune reprogramming, these exosomes drive the conversion of Treg to Th17, ultimately suppressing tumor growth (118). Furthermore, recent research demonstrates that engineered dendritic cell-derived exosomes (DEX) loaded with the chemokine XCL1 (DEX~XCL1~), in combination with cisplatin, facilitate the recruitment of conventional type 1 dendritic cells (cDC1; 3.8-fold increase) and enhance the proportion of activated CD8⁺ T cells to 61.27%. This strategy effectively converts the tumor microenvironment from an immunologically barren (“immune desert”) state into a T cell-enriched status, representing a promising “cold tumor” conversion approach (190). Collectively, these findings establish a triple immunomodulatory axis targeting exosomes: NK cell activation, macrophage reprogramming, and T cell suppression reversal, providing a mechanistic foundation for developing exosome-based combination immunotherapies.

Collectively, exosomes demonstrate significant therapeutic advantages for PCa through precision targeting capabilities and inherent biocompatibility. These vesicles enhance tumor-specific accumulation of chemotherapeutics or nucleic acid therapeutics to improve efficacy while simultaneously remodeling the immunosuppressive tumor microenvironment via engineered strategies—activating NK cells, reprogramming macrophages, and reversing T cell suppression (Figure 4). Substantial progress in clinical translation is evidenced by registered trials validating diagnostic applications: exosomal microRNA-based prognostic assessment of tumor aggressiveness (NCT03911999), urinary exosome gene signature validation (NCT02702856), and plasma exosomal RNA diagnostic system development (NCT06604130). These studies provide critical evidence bridging basic research and clinical implementation. However, three core challenges impede clinical adoption: payload heterogeneity requiring improved cargo loading efficiency and batch consistency; safety concerns regarding immunogenicity of surface modifications and off-target effects; and paradoxical pro-metastatic risks wherein tumor-derived exosomes may accelerate progression via metastasis-promoting factor transfer. Future advancement hinges on standardized isolation protocols, intelligent engineering platforms, and rigorous biosafety assessments to establish engineered exosomes as transformative tools for precision PCa therapy.

5.3 Barriers to clinical translation of exosomes in prostate cancer therapy

While exosome-based therapeutic strategies hold significant promise, their translation from fundamental prostate cancer research to clinical application is impeded by fundamental challenges in standardization, manufacturing, and quality control. A primary obstacle is the absence of uniform standards for production and characterization. Current isolation techniques—such as ultracentrifugation, precipitation, and size-exclusion chromatography—exhibit considerable variability in yield and purity. This methodological diversity results in poorly defined final products and substantial batch-to-batch heterogeneity, which in turn hinders the establishment of consistent regulatory evaluation frameworks and approval pathways. Furthermore, achieving scalable production under Good Manufacturing Practice (GMP) conditions remains a critical bottleneck. Conventional laboratory-scale methods relying on culture flasks and ultracentrifugation are not only inefficient and variable but also inadequate for meeting the demands of large-scale clinical-grade manufacturing. Although scalable technologies like hollow-fiber bioreactors are under exploration, their process development, control, and cost-effectiveness require further optimization.

Implementing a rigorous quality control (QC) system is paramount to ensuring consistent safety and efficacy. A comprehensive QC strategy spanning the entire production workflow must be established, encompassing: (1) Process Controls: Standardization of critical parameters including cell source, culture conditions, and harvest timing; (2) Product Characterization: Quantitative analysis of the physical properties, biochemical markers (e.g., CD9/63/81, while avoiding contaminant markers like Calnexin), and functional attributes of the final exosome preparation; (3) Release Testing: Confirmation that sterility, endotoxin levels, particle concentration, and biological potency meet predefined standards. Only through such a systematic “quality by design” approach can therapeutic exosomes evolve from laboratory curiosities into clinically viable and reliably effective medicinal products.

Patient heterogeneity must also be factored into quality assurance. As key carriers of metabolic and physiological information, exosome composition and function are markedly influenced by donor-specific factors. In PCa, patient characteristics such as age, androgen levels, castration-resistant status, and the presence of bone metastases can profoundly alter the miRNA, protein, or lipid profiles of circulating exosomes. This variability underscores the necessity of incorporating patient stratification and personalized strategies in the future clinical development of exosome-based therapies.

Moreover, while engineering exosomes can enhance their targeting capability or drug-loading efficiency, it may also introduce novel immunogenicity risks (191). These risks primarily stem from: (1) residual parental cell proteins in allogeneic sources; (2) exogenously expressed engineered proteins or peptides; (3) introduced therapeutic nucleic acids or chemical drugs. To advance clinical translation, developing effective immune evasion strategies is crucial. Current approaches focus on conferring “stealth” properties through surface engineering. For instance, overexpression of human CD47 can bind to SIRPα on macrophages, delivering a “don’t eat me” signal that significantly reduces clearance by the mononuclear phagocyte system and prolongs circulation half-life (192). Other strategies, such as PEGylation or camouflage using natural cell membranes, can also partially shield immunogenic epitopes. Using autologous cell sources for EV production fundamentally avoids immune rejection, though it presents its own scale-up challenges. Undoubtedly, any therapeutic exosome product must undergo stringent preclinical safety evaluations before entering clinical trials. This includes systematic assessment of toxicity, tumorigenicity, and immunogenicity in relevant animal models, coupled with comprehensive characterization following International Society for Extracellular Vesicles (ISEV) guidelines (193). Adherence to the principle of “safety by design” is the cornerstone for the successful translation of engineered exosomes.

6 Summary and outlook

Exosomes exhibit a dual nature in PCa—serving both as pathogenic mediators and therapeutic vehicles. Naturally occurring exosomes accelerate disease progression by transferring oncogenic cargo and mediating immunosuppression, whereas engineered modifications transform them into precision-targeted delivery systems for chemotherapeutics, nucleic acid drugs, and immunomodulators. The central paradox in clinical translation stems from their biological complexity: while targeting modifications enhance drug specificity, endogenous exosomal components may propagate metastatic risks; although immunomodulatory functions activate antitumor responses, they may concurrently induce immune escape. Resolving this requires interdisciplinary innovation: employing gene editing to eliminate pro-metastatic factors while preserving targeting capacity, developing stimuli-responsive biomaterials for spatiotemporally controlled release, and integrating liquid biopsy monitoring with imaging technologies to establish dynamic surveillance networks. Ultimately, exosome-based therapeutic strategies represent a paradigm shift toward curative interventions for PCa patients.

Author contributions

MY: Software, Writing – original draft, Visualization, Investigation. DZ: Writing – original draft, Investigation. HW: Software, Writing – original draft. TW: Writing – original draft, Visualization. JF: Writing – original draft, Visualization, Conceptualization. GR: Writing – review & editing, Visualization. CZ: Writing – review & editing, Writing – original draft, Supervision.

Funding

The author(s) declared that financial support was received for this work and/or its publication. This work was supported by the [Mechanisms of Papillary Thyroid Carcinogenesis: The Role of the Intratumoral Microbiota, Amino Acid Metabolism, and Innate Immunity Crosstalk Network] under Grant [FLKJ,2024AAN3049].

Conflict of interest

The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Generative AI statement

The author(s) declared that generative AI was not used in the creation of this manuscript.

Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Abbreviations

PCa, Prostate cancer; TME, tumor microenvironment; circRNA, circular ribonucleic acid; EGFR, epidermal growth factor receptor; ERK, extracellular signal-regulated kinase; ESCRT, endosomal sorting complex required for transport; GTPases, guanosine triphosphatases; MDSCs, Myeloid-derived suppressor cells;HSP, heat shock protein; ILV, intraluminal vesicle; lncRNA, long noncoding ribonucleic acid; MSC, mesenchymal stem cell; FAK, focal adhesion kinase; CAF, cancer-associated fibroblast; EMT, epithelial mesenchymal transition; MBV, multivesicular body; miRNAs, micro-ribonucleic acids; mRNA, messenger ribonucleic acids; hBMSCs, human bone marrow-derived mesenchymal stem cells; NK, natural killer cells; DCs,dendritic cells; DTX, docetaxel; AGO2,Argonaute 2;TEM, Transmission electron microscopy; NTA, Nanoparticle tracking analysis; WB, Western blot; FCM, Flow cytometry; ELISA,enzyme-linked immunosorbent assays.

References

1. Raychaudhuri R, Lin DW, and Montgomery RB. Prostate cancer: A review. Jama. (2025) 333:1433–46. doi: 10.1001/jama.2025.0228

PubMed Abstract | Crossref Full Text | Google Scholar

2. Zhang S, Zhang T, Kinsella GK, and Curtin JF. A review of the efficacy of prostate cancer therapies against castration-resistant prostate cancer. Drug Discov Today. (2025) 30:104384. doi: 10.1016/j.drudis.2025.104384

PubMed Abstract | Crossref Full Text | Google Scholar

3. Li X, Han Z, and Ai J. Synergistic targeting strategies for prostate cancer, Nature reviews. Urology. (2025) 22:645–71. doi: 10.1038/s41585-025-01042-6

PubMed Abstract | Crossref Full Text | Google Scholar

4. Kalluri R and LeBleu VS. The biology, function, and biomedical applications of exosomes. Science. (2020) 367. doi: 10.1126/science.aau6977

PubMed Abstract | Crossref Full Text | Google Scholar

5. Zheng Z, Zhai Y, Yan X, Wang Z, Zhang H, Xu R, et al. Functions and clinical applications of exosomes in gastric cancer. Int J Biol Sci. (2025) 21:2330–45. doi: 10.7150/ijbs.98087

PubMed Abstract | Crossref Full Text | Google Scholar

6. Mukerjee N, Bhattacharya A, Maitra S, Kaur M, Ganesan S, Mishra S, et al. Exosome isolation and characterization for advanced diagnostic and therapeutic applications, Materials today. Bio. (2025) 31:101613. doi: 10.1016/j.mtbio.2025.101613

PubMed Abstract | Crossref Full Text | Google Scholar

7. Jin Z, Zhang C, Shen L, and Cao Y. Harnessing exosomes: From tumor immune escape to therapeutic innovation in gastric cancer immunotherapy. Cancer Lett. (2025) 626:217792. doi: 10.1016/j.canlet.2025.217792

PubMed Abstract | Crossref Full Text | Google Scholar

8. Liu JJJ, Liu D, To SKY, and Wong AST. Exosomes in cancer nanomedicine: biotechnological advancements and innovations. Mol Cancer. (2025) 24:166. doi: 10.1186/s12943-025-02372-0

PubMed Abstract | Crossref Full Text | Google Scholar

9. Gao S, Dong Y, Yan C, Yu T, and Cao H. The role of exosomes and exosomal microRNA in diabetic cardiomyopathy. Front Endocrinol. (2023) 14:1327495. doi: 10.3389/fendo.2023.1327495

PubMed Abstract | Crossref Full Text | Google Scholar

10. Kalluri R. The biology and function of extracellular vesicles in immune response and immunity. Immunity. (2024) 57:1752–68. doi: 10.1016/j.immuni.2024.07.009

PubMed Abstract | Crossref Full Text | Google Scholar

11. Feng J, Zhang Y, Zhu Z, Gu C, Waqas A, and Chen L. Emerging exosomes and exosomal miRNAs in spinal cord injury. Front Cell Dev Biol. (2021) 9:703989. doi: 10.3389/fcell.2021.703989

PubMed Abstract | Crossref Full Text | Google Scholar

12. Marsh M and van Meer G. Cell biology. No ESCRTs for exosomes. Science. (2008) 319:1191–2. doi: 10.1126/science.1155750

PubMed Abstract | Crossref Full Text | Google Scholar

13. Zheng D, Huo M, Li B, Wang W, Piao H, Wang Y, et al. The role of exosomes and exosomal microRNA in cardiovascular disease. Front Cell Dev Biol. (2020) 8:616161. doi: 10.3389/fcell.2020.616161

PubMed Abstract | Crossref Full Text | Google Scholar

14. Schmidt O and Teis D. The ESCRT machinery. Curr biology: CB. (2012) 22:R116–20. doi: 10.1016/j.cub.2012.01.028

PubMed Abstract | Crossref Full Text | Google Scholar

15. Stuffers S, Sem Wegner C, Stenmark H, and Brech A. Multivesicular endosome biogenesis in the absence of ESCRTs. Traffic (Copenhagen Denmark). (2009) 10:925–37. doi: 10.1111/j.1600-0854.2009.00920.x

PubMed Abstract | Crossref Full Text | Google Scholar

16. Choezom D and Gross JC. Neutral sphingomyelinase 2 controls exosome secretion by counteracting V-ATPase-mediated endosome acidification. J Cell Sci. (2022) 135. doi: 10.1242/jcs.259324

PubMed Abstract | Crossref Full Text | Google Scholar

17. van Niel G, Charrin S, Simoes S, Romao M, Rochin L, Saftig P, et al. The tetraspanin CD63 regulates ESCRT-independent and -dependent endosomal sorting during melanogenesis. Dev Cell. (2011) 21:708–21. doi: 10.1016/j.devcel.2011.08.019

PubMed Abstract | Crossref Full Text | Google Scholar

18. Chairoungdua A, Smith DL, Pochard P, Hull M, and Caplan MJ. Exosome release of β-catenin: a novel mechanism that antagonizes Wnt signaling. J Cell Biol. (2010) 190:1079–91. doi: 10.1083/jcb.201002049

PubMed Abstract | Crossref Full Text | Google Scholar

19. Wang J, Xia J, Huang R, Hu Y, Fan J, Shu Q, et al. Mesenchymal stem cell-derived extracellular vesicles alter disease outcomes via endorsement of macrophage polarization. Stem Cell Res Ther. (2020) 11:424. doi: 10.1186/s13287-020-01937-8

PubMed Abstract | Crossref Full Text | Google Scholar

20. Keshtkar S, Azarpira N, and Ghahremani MH. Mesenchymal stem cell-derived extracellular vesicles: novel frontiers in regenerative medicine. Stem Cell Res Ther. (2018) 9:63. doi: 10.1186/s13287-018-0791-7

PubMed Abstract | Crossref Full Text | Google Scholar

21. Yu Z, Fu J, Mantareva V, Blažević I, Wu Y, Wen D, et al. The role of tumor-derived exosomal LncRNA in tumor metastasis. Cancer Gene Ther. (2025) 32:273–85. doi: 10.1038/s41417-024-00852-x

PubMed Abstract | Crossref Full Text | Google Scholar

22. Perrone MG, Filieri S, Azzariti A, Armenise D, Baldelli OM, Liturri A, et al. Exosomes in ovarian cancer: towards precision oncology. Pharmaceuticals. (2025) 18:371. doi: 10.3390/ph18030371

PubMed Abstract | Crossref Full Text | Google Scholar

23. Zhang Q, Wang H, Liu Q, Zeng N, Fu G, Qiu Y, et al. Exosomes as powerful biomarkers in cancer: recent advances in isolation and detection techniques. Int J nanomedicine. (2024) 19:1923–49. doi: 10.2147/IJN.S453545

PubMed Abstract | Crossref Full Text | Google Scholar

24. Shen J, Ma Z, Xu J, Xue T, Lv X, Zhu G, et al. Exosome isolation and detection: from microfluidic chips to nanoplasmonic biosensor. ACS Appl Mater Interfaces. (2024) 16:22776–93. doi: 10.1021/acsami.3c19396

PubMed Abstract | Crossref Full Text | Google Scholar

25. Lai JJ, Chau ZL, Chen SY, Hill JJ, Korpany KV, Liang NW, et al. Exosome processing and characterization approaches for research and technology development. Adv Sci (Weinh). (2022) 9:e2103222. doi: 10.1002/advs.202103222

PubMed Abstract | Crossref Full Text | Google Scholar

26. He L, Zhu D, Wang J, and Wu X. A highly efficient method for isolating urinary exosomes. Int J Mol Med. (2019) 43:83–90. doi: 10.3892/ijmm.2018.3944

PubMed Abstract | Crossref Full Text | Google Scholar

27. Yousif G, Qadri S, Parray A, Akhthar N, Shuaib A, and Haik Y. Exosomes derived neuronal markers: immunoaffinity isolation and characterization. Neuromolecular Med. (2022) 24:339–51. doi: 10.1007/s12017-021-08696-6

PubMed Abstract | Crossref Full Text | Google Scholar

28. Sidhom K, Obi PO, and Saleem A. A review of exosomal isolation methods: is size exclusion chromatography the best option? Int J Mol Sci. (2020) 21. doi: 10.3390/ijms21186466

PubMed Abstract | Crossref Full Text | Google Scholar

29. Lee H, Lee J, Ko M, Lee KN, Kim Y, Seo B, et al. Advanced exosome isolation through electrophoretic oscillation-assisted tangent-flow ultrafiltration with a PVDF-fiber-coated siN(x) nanofilter. ACS Appl Bio materials. (2025) 8:2965–76. doi: 10.1021/acsabm.4c01821

PubMed Abstract | Crossref Full Text | Google Scholar

30. Omrani M, Beyrampour-Basmenj H, Jahanban-Esfahlan R, Talebi M, Raeisi M, Serej ZA, et al. Global trend in exosome isolation and application: an update concept in management of diseases. Mol Cell Biochem. (2024) 479:679–91. doi: 10.1007/s11010-023-04756-6

PubMed Abstract | Crossref Full Text | Google Scholar

31. Dong B, Wang C, Zhang J, Zhang J, Gu Y, Guo X, et al. Exosomes from human umbilical cord mesenchymal stem cells attenuate the inflammation of severe steroid-resistant asthma by reshaping macrophage polarization. Stem Cell Res Ther. (2021) 12:204. doi: 10.1186/s13287-021-02244-6

PubMed Abstract | Crossref Full Text | Google Scholar

32. T LR, Sánchez-Abarca LI, Muntión S, Preciado S, Puig N, López-Ruano G, et al. MSC surface markers (CD44, CD73, and CD90) can identify human MSC-derived extracellular vesicles by conventional flow cytometry. Cell communication signaling: CCS. (2016) 14:2. doi: 10.1186/s12964-015-0124-8

PubMed Abstract | Crossref Full Text | Google Scholar

33. Siwaponanan P, Kaewkumdee P, Phromawan W, Udompunturak S, Chomanee N, Udol K, et al. Increased expression of six-large extracellular vesicle-derived miRNAs signature for nonvalvular atrial fibrillation. J Trans Med. (2022) 20:4. doi: 10.1186/s12967-021-03213-6

PubMed Abstract | Crossref Full Text | Google Scholar

34. Lozano-Andrés E, Libregts SF, Toribio V, Royo F, Morales S, López-Martín S, et al. Tetraspanin-decorated extracellular vesicle-mimetics as a novel adaptable reference material. J extracellular vesicles. (2019) 8:1573052. doi: 10.1080/20013078.2019.1573052

PubMed Abstract | Crossref Full Text | Google Scholar

35. Kamei N, Nishimura H, Matsumoto A, Asano R, Muranaka K, Fujita M, et al. Comparative study of commercial protocols for high recovery of high-purity mesenchymal stem cell-derived extracellular vesicle isolation and their efficient labeling with fluorescent dyes. Nanomedicine: nanotechnology biology Med. (2021) 35:102396. doi: 10.1016/j.nano.2021.102396

PubMed Abstract | Crossref Full Text | Google Scholar

36. Hu Z, Chen G, Zhao Y, Gao H, Li L, Yin Y, et al. Exosome-derived circCCAR1 promotes CD8 + T-cell dysfunction and anti-PD1 resistance in hepatocellular carcinoma. Mol Cancer. (2023) 22:55. doi: 10.1186/s12943-023-01759-1

PubMed Abstract | Crossref Full Text | Google Scholar

37. Pan J, Ding M, Xu K, Yang C, and Mao LJ. Exosomes in diagnosis and therapy of prostate cancer. Oncotarget. (2017) 8:97693–700. doi: 10.18632/oncotarget.18532

PubMed Abstract | Crossref Full Text | Google Scholar

38. Pastushenko I and Blanpain C. EMT transition states during tumor progression and metastasis. Trends Cell Biol. (2019) 29:212–26. doi: 10.1016/j.tcb.2018.12.001

PubMed Abstract | Crossref Full Text | Google Scholar

39. Gaballa R, Ali HEA, Mahmoud MO, Rhim JS, Ali HI, Salem HF, et al. Exosomes-mediated transfer of itga2 promotes migration and invasion of prostate cancer cells by inducing epithelial-mesenchymal transition. Cancers (Basel). (2020) 12. doi: 10.3390/cancers12082300

PubMed Abstract | Crossref Full Text | Google Scholar

40. Li Y, Li Q, Gu J, Qian D, Qin X, and Li D. Exosomal prostate-specific G-protein-coupled receptor induces osteoblast activity to promote the osteoblastic metastasis of prostate cancer. Trans Cancer Res. (2020) 9:5857–67. doi: 10.21037/tcr-20-1858

PubMed Abstract | Crossref Full Text | Google Scholar

41. Lin CJ, Yun EJ, Lo UG, Tai YL, Deng S, Hernandez E, et al. The paracrine induction of prostate cancer progression by caveolin-1. Cell Death Dis. (2019) 10:834. doi: 10.1038/s41419-019-2066-3

PubMed Abstract | Crossref Full Text | Google Scholar

42. Li Y, Li Q, Li D, Gu J, Qian D, Qin X, et al. Exosome carrying PSGR promotes stemness and epithelial-mesenchymal transition of low aggressive prostate cancer cells. Life Sci. (2021) 264:118638. doi: 10.1016/j.lfs.2020.118638

PubMed Abstract | Crossref Full Text | Google Scholar

43. Zhou C, Chen Y, He X, Zheng Z, and Xue D. Functional Implication of Exosomal miR-217 and miR-23b-3p in the Progression of Prostate Cancer. OncoTargets Ther. (2020) 13:11595–606. doi: 10.2147/OTT.S272869

PubMed Abstract | Crossref Full Text | Google Scholar

44. Josson S, Gururajan M, Hu P, Shao C, Chu GY, Zhau HE, et al. miR-409-3p/-5p promotes tumorigenesis, epithelial-to-mesenchymal transition, and bone metastasis of human prostate cancer. Clin Cancer Res. (2014) 20:4636–46. doi: 10.1158/1078-0432.CCR-14-0305

PubMed Abstract | Crossref Full Text | Google Scholar

45. Zhang G, Liu Y, Yang J, Wang H, and Xing Z. Inhibition of circ_0081234 reduces prostate cancer tumor growth and metastasis via the miR-1/MAP 3 K1 axis. J Gene Med. (2022) 24:e3376. doi: 10.1002/jgm.3376

PubMed Abstract | Crossref Full Text | Google Scholar

46. Wei Y, Chen Z, Zhang R, Wu B, Lin L, Zhu Q, et al. Blood circulating exosomes carrying microRNA-423-5p regulates cell progression in prostate cancer via targeting FRMD3. J Cancer. (2022) 13:2970–81. doi: 10.7150/jca.71706

PubMed Abstract | Crossref Full Text | Google Scholar

47. Zhang Y, Zhao J, Ding M, Su Y, Cui D, Jiang C, et al. Loss of exosomal miR-146a-5p from cancer-associated fibroblasts after androgen deprivation therapy contributes to prostate cancer metastasis. J Exp Clin Cancer Res. (2020) 39:282. doi: 10.1186/s13046-020-01761-1

PubMed Abstract | Crossref Full Text | Google Scholar

48. Atri Roozbahani G, Kokal-Ribaudo M, Heidari Horestani M, Pungsrinont T, and Baniahmad A. The protein composition of exosomes released by prostate cancer cells is distinctly regulated by androgen receptor-antagonists and -agonist to stimulate growth of target cells. Cell communication signaling: CCS. (2024) 22:219. doi: 10.1186/s12964-024-01584-z

PubMed Abstract | Crossref Full Text | Google Scholar

49. DeRita RM, Zerlanko B, Singh A, Lu H, Iozzo RV, Benovic JL, et al. c-src, insulin-like growth factor I receptor, G-protein-coupled receptor kinases and focal adhesion kinase are enriched into prostate cancer cell exosomes. J Cell Biochem. (2017) 118:66–73. doi: 10.1002/jcb.25611

PubMed Abstract | Crossref Full Text | Google Scholar

50. Deep G, Jain A, Kumar A, Agarwal C, Kim S, Leevy WM, et al. Exosomes secreted by prostate cancer cells under hypoxia promote matrix metalloproteinases activity at pre-metastatic niches. Mol carcinogenesis. (2020) 59:323–32. doi: 10.1002/mc.23157

PubMed Abstract | Crossref Full Text | Google Scholar

51. Prigol AN, Rode MP, Silva AH, Cisilotto J, and Creczynski-Pasa TB. Pro-angiogenic effect of PC-3 exosomes in endothelial cells in vitro. Cell signalling. (2021) 87:110126. doi: 10.1016/j.cellsig.2021.110126

PubMed Abstract | Crossref Full Text | Google Scholar

52. Liu P, Wang W, Wang F, Fan J, Guo J, Wu T, et al. Alterations of plasma exosomal proteins and motabolies are associated with the progression of castration-resistant prostate cancer. J Trans Med. (2023) 21:40. doi: 10.1186/s12967-022-03860-3

PubMed Abstract | Crossref Full Text | Google Scholar

53. Luo JQ, Yang TW, Wu J, Lai HH, Zou LB, Chen WB, et al. Exosomal PGAM1 promotes prostate cancer angiogenesis and metastasis by interacting with ACTG1. Cell Death Dis. (2023) 14:502. doi: 10.1038/s41419-023-06007-4

PubMed Abstract | Crossref Full Text | Google Scholar

54. Ioannidou E, Moschetta M, Shah S, Parker JS, Ozturk MA, Pappas-Gogos G, et al. Angiogenesis and anti-angiogenic treatment in prostate cancer: mechanisms of action and molecular targets. Int J Mol Sci. (2021) 22. doi: 10.3390/ijms22189926

PubMed Abstract | Crossref Full Text | Google Scholar

55. Sporn MB. The war on cancer. Lancet (London England). (1996) 347:1377–81. doi: 10.1016/S0140-6736(96)91015-6

PubMed Abstract | Crossref Full Text | Google Scholar

56. Wee I, Syn N, Sethi G, Goh BC, and Wang L. Role of tumor-derived exosomes in cancer metastasis, Biochimica et biophysica acta. Rev Cancer. (2019) 1871:12–9. doi: 10.1016/j.bbcan.2018.10.004

PubMed Abstract | Crossref Full Text | Google Scholar

57. Yin L, Liu X, Shao X, Feng T, Xu J, Wang Q, et al. The role of exosomes in lung cancer metastasis and clinical applications: an updated review. J Trans Med. (2021) 19:312. doi: 10.1186/s12967-021-02985-1

PubMed Abstract | Crossref Full Text | Google Scholar

58. Yu L, Sui B, Fan W, Lei L, Zhou L, Yang L, et al. Exosomes derived from osteogenic tumor activate osteoclast differentiation and concurrently inhibit osteogenesis by transferring COL1A1-targeting miRNA-92a-1-5p. J extracellular vesicles. (2021) 10:e12056. doi: 10.1002/jev2.12056

PubMed Abstract | Crossref Full Text | Google Scholar

59. Duan Y, Tan Z, Yang M, Li J, Liu C, Wang C, et al. PC-3-derived exosomes inhibit osteoclast differentiation by downregulating miR-214 and blocking NF-κB signaling pathway. BioMed Res Int. (2019) 2019:8650846. doi: 10.1155/2019/8650846

PubMed Abstract | Crossref Full Text | Google Scholar

60. Liu Y, Yang C, Chen S, Liu W, Liang J, He S, et al. Cancer-derived exosomal miR-375 targets DIP2C and promotes osteoblastic metastasis and prostate cancer progression by regulating the Wnt signaling pathway. Cancer Gene Ther. (2023) 30:437–49. doi: 10.1038/s41417-022-00563-1

PubMed Abstract | Crossref Full Text | Google Scholar

61. Zou Z, Dai R, Deng N, Su W, and Liu P. Exosomal miR-1275 secreted by prostate cancer cells modulates osteoblast proliferation and activity by targeting the SIRT2/RUNX2 cascade. Cell Transplant. (2021) 30:9636897211052977. doi: 10.1177/09636897211052977

PubMed Abstract | Crossref Full Text | Google Scholar

62. Mo C, Huang B, Zhuang J, Jiang S, Guo S, and Mao X. LncRNA nuclear-enriched abundant transcript 1 shuttled by prostate cancer cells-secreted exosomes initiates osteoblastic phenotypes in the bone metastatic microenvironment via miR-205-5p/runt-related transcription factor 2/splicing factor proline- and glutamine-rich/polypyrimidine tract-binding protein 2 axis. Clin Trans Med. (2021) 11:e493. doi: 10.1002/ctm2.493

PubMed Abstract | Crossref Full Text | Google Scholar

63. Li SL, An N, Liu B, Wang SY, Wang JJ, and Ye Y. Exosomes from LNCaP cells promote osteoblast activity through miR-375 transfer. Oncol Lett. (2019) 17:4463–73. doi: 10.3892/ol.2019.10110

PubMed Abstract | Crossref Full Text | Google Scholar

64. Cruz-Burgos M, Cortés-Ramírez SA, Losada-García A, Morales-Pacheco M, Martínez-Martínez E, Morales-Montor JG, et al. Unraveling the role of EV-derived miR-150-5p in prostate cancer metastasis and its association with high-grade gleason scores: implications for diagnosis. Cancers. (2023) 15. doi: 10.3390/cancers15164148

PubMed Abstract | Crossref Full Text | Google Scholar

65. Rajagopal C and Harikumar KB. The origin and functions of exosomes in cancer. Front Oncol. (2018) 8:66. doi: 10.3389/fonc.2018.00066

PubMed Abstract | Crossref Full Text | Google Scholar

66. Malla B, Zaugg K, Vassella E, Aebersold DM, and Dal Pra A. Exosomes and exosomal microRNAs in prostate cancer radiation therapy. Int J Radiat oncology biology Phys. (2017) 98:982–95. doi: 10.1016/j.ijrobp.2017.03.031

PubMed Abstract | Crossref Full Text | Google Scholar

67. Ding L, Zheng Q, Lin Y, Wang R, Wang H, Luo W, et al. Exosome-derived circTFDP2 promotes prostate cancer progression by preventing PARP1 from caspase-3-dependent cleavage. Clin Trans Med. (2023) 13:e1156. doi: 10.1002/ctm2.1156

PubMed Abstract | Crossref Full Text | Google Scholar

68. Gao F, Xu Q, Tang Z, Zhang N, Huang Y, Li Z, et al. Exosomes derived from myeloid-derived suppressor cells facilitate castration-resistant prostate cancer progression via S100A9/circMID1/miR-506-3p/MID1. J Trans Med. (2022) 20:346. doi: 10.1186/s12967-022-03494-5

PubMed Abstract | Crossref Full Text | Google Scholar

69. Han Q, Xie QR, Li F, Cheng Y, Wu T, Zhang Y, et al. Targeted inhibition of SIRT6 via engineered exosomes impairs tumorigenesis and metastasis in prostate cancer. Theranostics. (2021) 11:6526–41. doi: 10.7150/thno.53886

PubMed Abstract | Crossref Full Text | Google Scholar

70. Bánová Vulić R, Zdurienčíková M, Tyčiaková S, Benada O, Dubrovčáková M, Lakota J, et al. Silencing of carbonic anhydrase I enhances the Malignant potential of exosomes secreted by prostatic tumour cells. J Cell Mol Med. (2019) 23:3641–55. doi: 10.1111/jcmm.14265

PubMed Abstract | Crossref Full Text | Google Scholar

71. Dai Y and Gao X. Inhibition of cancer cell-derived exosomal microRNA-183 suppresses cell growth and metastasis in prostate cancer by upregulating TPM1. Cancer Cell Int. (2021) 21:145. doi: 10.1186/s12935-020-01686-x

PubMed Abstract | Crossref Full Text | Google Scholar

72. Liu Z, Lin Z, Jiang M, Zhu G, Xiong T, Cao F, et al. Cancer-associated fibroblast exosomes promote prostate cancer metastasis through miR-500a-3p/FBXW7/HSF1 axis under hypoxic microenvironment. Cancer Gene Ther. (2024) 31:698–709. doi: 10.1038/s41417-024-00742-2

PubMed Abstract | Crossref Full Text | Google Scholar

73. Wang S, Du P, Cao Y, Ma J, Yang X, Yu Z, et al. Cancer associated fibroblasts secreted exosomal miR-1290 contributes to prostate cancer cell growth and metastasis via targeting GSK3β. Cell Death Discov. (2022) 8:371. doi: 10.1038/s41420-022-01163-6

PubMed Abstract | Crossref Full Text | Google Scholar

74. Fabbri M, Paone A, Calore F, Galli R, Gaudio E, Santhanam R, et al. MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response. Proc Natl Acad Sci U.S.A. (2012) 109:E2110–6. doi: 10.1073/pnas.1209414109

PubMed Abstract | Crossref Full Text | Google Scholar

75. Zhou X, Jia Y, Mao C, and Liu S. Small extracellular vesicles: Non-negligible vesicles in tumor progression, diagnosis, and therapy. Cancer Lett. (2024) 580:216481. doi: 10.1016/j.canlet.2023.216481

PubMed Abstract | Crossref Full Text | Google Scholar

76. Ramteke A, Ting H, Agarwal C, Mateen S, Somasagara R, Hussain A, et al. Exosomes secreted under hypoxia enhance invasiveness and stemness of prostate cancer cells by targeting adherens junction molecules. Mol carcinogenesis. (2015) 54:554–65. doi: 10.1002/mc.22124

PubMed Abstract | Crossref Full Text | Google Scholar

77. Abd Elmageed ZY, Yang Y, Thomas R, Ranjan M, Mondal D, Moroz K, et al. Neoplastic reprogramming of patient-derived adipose stem cells by prostate cancer cell-associated exosomes. Stem Cells (Dayton Ohio). (2014) 32:983–97. doi: 10.1002/stem.1619

PubMed Abstract | Crossref Full Text | Google Scholar

78. McAtee CO, Booth C, Elowsky C, Zhao L, Payne J, Fangman T, et al. Prostate tumor cell exosomes containing hyaluronidase Hyal1 stimulate prostate stromal cell motility by engagement of FAK-mediated integrin signaling. Matrix biology: J Int Soc Matrix Biol. (2019) 78-79:165–79. doi: 10.1016/j.matbio.2018.05.002

PubMed Abstract | Crossref Full Text | Google Scholar

79. Muñoz-Moreno L, Carmena MJ, Schally AV, Prieto JC, and Bajo AM. Stimulation of neuroendocrine differentiation in prostate cancer cells by GHRH and its blockade by GHRH antagonists. Investigational New Drugs. (2020) 38:746–54. doi: 10.1007/s10637-019-00831-2

PubMed Abstract | Crossref Full Text | Google Scholar

80. Lin LC, Gao AC, Lai CH, Hsieh JT, and Lin H. Induction of neuroendocrine differentiation in castration resistant prostate cancer cells by adipocyte differentiation-related protein (ADRP) delivered by exosomes. Cancer Lett. (2017) 391:74–82. doi: 10.1016/j.canlet.2017.01.018

PubMed Abstract | Crossref Full Text | Google Scholar

81. Bhagirath D, Yang TL, Tabatabai ZL, Majid S, Dahiya R, Tanaka Y, et al. BRN4 is a novel driver of neuroendocrine differentiation in castration-resistant prostate cancer and is selectively released in extracellular vesicles with BRN2. Clin Cancer Res. (2019) 25:6532–45. doi: 10.1158/1078-0432.CCR-19-0498

PubMed Abstract | Crossref Full Text | Google Scholar

82. Abusamra AJ, Zhong Z, Zheng X, Li M, Ichim TE, Chin JL, et al. Tumor exosomes expressing Fas ligand mediate CD8+ T-cell apoptosis. Blood cells molecules Dis. (2005) 35:169–73. doi: 10.1016/j.bcmd.2005.07.001

PubMed Abstract | Crossref Full Text | Google Scholar

83. Xu F, Wang X, Huang Y, Zhang X, Sun W, Du Y, et al. Prostate cancer cell-derived exosomal IL-8 fosters immune evasion by disturbing glucolipid metabolism of CD8(+) T cell. Cell Rep. (2023) 42:113424. doi: 10.1016/j.celrep.2023.113424

PubMed Abstract | Crossref Full Text | Google Scholar

84. Lundholm M, Schröder M, Nagaeva O, Baranov V, Widmark A, Mincheva-Nilsson L, et al. Prostate tumor-derived exosomes down-regulate NKG2D expression on natural killer cells and CD8+ T cells: mechanism of immune evasion. PloS One. (2014) 9:e108925. doi: 10.1371/journal.pone.0108925

PubMed Abstract | Crossref Full Text | Google Scholar

85. Salimu J, Webber J, Gurney M, Al-Taei S, Clayton A, and Tabi Z. Dominant immunosuppression of dendritic cell function by prostate-cancer-derived exosomes. J extracellular vesicles. (2017) 6:1368823. doi: 10.1080/20013078.2017.1368823

PubMed Abstract | Crossref Full Text | Google Scholar

86. Guan H, Mao L, Wang J, Wang S, Yang S, Wu H, et al. Exosomal RNF157 mRNA from prostate cancer cells contributes to M2 macrophage polarization through destabilizing HDAC1. Front Oncol. (2022) 12:1021270. doi: 10.3389/fonc.2022.1021270

PubMed Abstract | Crossref Full Text | Google Scholar

87. Xu W, Lu M, Xie S, Zhou D, Zhu M, and Liang C. Endoplasmic reticulum stress promotes prostate cancer cells to release exosome and up-regulate PD-L1 expression via PI3K/akt signaling pathway in macrophages. J Cancer. (2023) 14:1062–74. doi: 10.7150/jca.81933

PubMed Abstract | Crossref Full Text | Google Scholar

88. Li N, Wang Y, Xu H, Wang H, Gao Y, and Zhang Y. Exosomes Derived from RM-1 Cells Promote the Recruitment of MDSCs into Tumor Microenvironment by Upregulating CXCR4 via TLR2/NF-κB Pathway. J Oncol. (2021) 2021:5584406. doi: 10.1155/2021/5584406

PubMed Abstract | Crossref Full Text | Google Scholar

89. Öhlund D, Elyada E, and Tuveson D. Fibroblast heterogeneity in the cancer wound. J Exp Med. (2014) 211:1503–23. doi: 10.1084/jem.20140692

PubMed Abstract | Crossref Full Text | Google Scholar

90. Naito Y, Yoshioka Y, Yamamoto Y, and Ochiya T. How cancer cells dictate their microenvironment: present roles of extracellular vesicles. Cell Mol Life sciences: CMLS. (2017) 74:697–713. doi: 10.1007/s00018-016-2346-3

PubMed Abstract | Crossref Full Text | Google Scholar

91. Webber J, Steadman R, Mason MD, Tabi Z, and Clayton A. Cancer exosomes trigger fibroblast to myofibroblast differentiation. Cancer Res. (2010) 70:9621–30. doi: 10.1158/0008-5472.CAN-10-1722

PubMed Abstract | Crossref Full Text | Google Scholar

92. Yang X and Qian K. Protein O-GlcNAcylation: emerging mechanisms and functions. Nat Rev Mol Cell Biol. (2017) 18:452–65. doi: 10.1038/nrm.2017.22

PubMed Abstract | Crossref Full Text | Google Scholar

93. Cui D, Li J, Zhu Z, Berk M, Hardaway A, McManus J, et al. Cancer-associated fibroblast-secreted glucosamine alters the androgen biosynthesis program in prostate cancer via HSD3B1 upregulation. J Clin Invest. (2023) 133. doi: 10.1172/JCI161913

PubMed Abstract | Crossref Full Text | Google Scholar

94. Milman N, Ginini L, and Gil Z. Exosomes and their role in tumorigenesis and anticancer drug resistance. Drug resistance updates: Rev commentaries antimicrobial Anticancer chemotherapy. (2019) 45:1–12. doi: 10.1016/j.drup.2019.07.003

PubMed Abstract | Crossref Full Text | Google Scholar

95. Kharaziha P, Chioureas D, Rutishauser D, Baltatzis G, Lennartsson L, Fonseca P, et al. Molecular profiling of prostate cancer derived exosomes may reveal a predictive signature for response to docetaxel. Oncotarget. (2015) 6:21740–54. doi: 10.18632/oncotarget.3226

PubMed Abstract | Crossref Full Text | Google Scholar

96. Mashouri L, Yousefi H, Aref AR, Ahadi AM, Molaei F, and Alahari SK. Exosomes: composition, biogenesis, and mechanisms in cancer metastasis and drug resistance. Mol Cancer. (2019) 18:75. doi: 10.1186/s12943-019-0991-5

PubMed Abstract | Crossref Full Text | Google Scholar

97. Corcoran C, Rani S, and O’Driscoll L. miR-34a is an intracellular and exosomal predictive biomarker for response to docetaxel with clinical relevance to prostate cancer progression. Prostate. (2014) 74:1320–34. doi: 10.1002/pros.22848

PubMed Abstract | Crossref Full Text | Google Scholar

98. Li J, Yang X, Guan H, Mizokami A, Keller ET, Xu X, et al. Exosome-derived microRNAs contribute to prostate cancer chemoresistance. Int J Oncol. (2016) 49:838–46. doi: 10.3892/ijo.2016.3560

PubMed Abstract | Crossref Full Text | Google Scholar

99. Cao Z, Xu L, and Zhao S. Exosome-derived miR-27a produced by PSC-27 cells contributes to prostate cancer chemoresistance through p53. Biochem Biophys Res Commun. (2019) 515:345–51. doi: 10.1016/j.bbrc.2019.05.120

PubMed Abstract | Crossref Full Text | Google Scholar

100. Zhao J, Shen J, Mao L, Yang T, Liu J, and Hongbin S. Cancer associated fibroblast secreted miR-432-5p targets CHAC1 to inhibit ferroptosis and promote acquired chemoresistance in prostate cancer. Oncogene. (2024) 43:2104–14. doi: 10.1038/s41388-024-03057-6

PubMed Abstract | Crossref Full Text | Google Scholar

101. Shan G, Gu J, Zhou D, Li L, Cheng W, Wang Y, et al. Cancer-associated fibroblast-secreted exosomal miR-423-5p promotes chemotherapy resistance in prostate cancer by targeting GREM2 through the TGF-β signaling pathway. Exp Mol Med. (2020) 52:1809–22. doi: 10.1038/s12276-020-0431-z

PubMed Abstract | Crossref Full Text | Google Scholar

102. Corcoran C, Rani S, O’Brien K, O’Neill A, Prencipe M, Sheikh R, et al. Docetaxel-resistance in prostate cancer: evaluating associated phenotypic changes and potential for resistance transfer via exosomes. PloS One. (2012) 7:e50999. doi: 10.1371/journal.pone.0050999

PubMed Abstract | Crossref Full Text | Google Scholar

103. Kato T, Mizutani K, Kameyama K, Kawakami K, Fujita Y, Nakane K, et al. Serum exosomal P-glycoprotein is a potential marker to diagnose docetaxel resistance and select a taxoid for patients with prostate cancer. Urol Oncol. (2015) 33:385.e15–20. doi: 10.1016/j.urolonc.2015.04.019

PubMed Abstract | Crossref Full Text | Google Scholar

104. Lin A, Li J, and He W. CircSLC4A7 in resistant-cells-derived exosomes promotes docetaxel resistance via the miR-1205/MAPT axis in prostate cancer. IUBMB Life. (2024) 76:1342–55. doi: 10.1002/iub.2915

PubMed Abstract | Crossref Full Text | Google Scholar

105. Zhang H, Li M, Zhang J, Shen Y, and Gui Q. Exosomal circ-XIAP promotes docetaxel resistance in prostate cancer by regulating miR-1182/TPD52 axis. Drug design Dev Ther. (2021) 15:1835–49. doi: 10.2147/DDDT.S300376

PubMed Abstract | Crossref Full Text | Google Scholar

106. Tan X, Song X, Fan B, Li M, Zhang A, and Pei L. Exosomal circRNA Scm-like with four Malignant brain tumor domains 2 (circ-SFMBT2) enhances the docetaxel resistance of prostate cancer via the microRNA-136-5p/tribbles homolog 1 pathway. Anti-cancer Drugs. (2022) 33:871–82. doi: 10.1097/CAD.0000000000001365

PubMed Abstract | Crossref Full Text | Google Scholar

107. Jiang X, Xu Y, Liu R, and Guo S. Exosomal lincROR Promotes Docetaxel Resistance in Prostate Cancer through a β-catenin/HIF1α Positive Feedback Loop. Mol Cancer research: MCR. (2023) 21:472–82. doi: 10.1158/1541-7786.MCR-22-0458

PubMed Abstract | Crossref Full Text | Google Scholar

108. Zhang Z, Karthaus WR, Lee YS, Gao VR, Wu C, Russo JW, et al. Tumor microenvironment-derived NRG1 promotes antiandrogen resistance in prostate cancer. Cancer Cell. (2020) 38:279–296.e9. doi: 10.1016/j.ccell.2020.06.005

PubMed Abstract | Crossref Full Text | Google Scholar

109. Wang C, Zhou C, Wang D, Zhang YF, Lv HX, He H, et al. Proangiogenic potential of plasma exosomes from prostate cancer patients. Cell signalling. (2024) 124:111398. doi: 10.1016/j.cellsig.2024.111398

PubMed Abstract | Crossref Full Text | Google Scholar

110. Wang X, Wang X, Zhu Z, Li W, Yu G, Jia Z, et al. Prostate carcinoma cell-derived exosomal MicroRNA-26a modulates the metastasis and tumor growth of prostate carcinoma. Biomedicine pharmacotherapy = Biomedecine pharmacotherapie. (2019) 117:109109. doi: 10.1016/j.biopha.2019.109109

PubMed Abstract | Crossref Full Text | Google Scholar

111. Tian G, Hu K, Qiu S, Xie Y, Cao Y, Ni S, et al. Exosomes derived from PC-3 cells suppress osteoclast differentiation by downregulating miR-148a and blocking the PI3K/AKT/mTOR pathway. Exp Ther Med. (2021) 22:1304. doi: 10.3892/etm.2021.10739

PubMed Abstract | Crossref Full Text | Google Scholar

112. Tang Y, Liu J, Li X, and Wang W. Exosomal circRNA HIPK3 knockdown inhibited cell proliferation and metastasis in prostate cancer by regulating miR-212/BMI-1 pathway. J Biosci. (2021) 46. doi: 10.1007/s12038-021-00190-2

PubMed Abstract | Crossref Full Text | Google Scholar

113. Honeywell DR, Cabrita MA, Zhao H, Dimitroulakos J, and Addison CL. miR-105 inhibits prostate tumour growth by suppressing CDK6 levels. PloS One. (2013) 8:e70515. doi: 10.1371/journal.pone.0070515

PubMed Abstract | Crossref Full Text | Google Scholar

114. Han Z, Yi X, Li J, Zhang T, Liao D, You J, et al. RNA m(6)A modification in prostate cancer: A new weapon for its diagnosis and therapy, Biochimica et biophysica acta. Rev Cancer. (2023) 1878:188961. doi: 10.1016/j.bbcan.2023.188961

PubMed Abstract | Crossref Full Text | Google Scholar

115. Wu T, Zhang Y, Han Q, Lu X, Cheng Y, Chen J, et al. Klotho-beta attenuates Rab8a-mediated exosome regulation and promotes prostate cancer progression. Oncogene. (2023) 42:2801–15. doi: 10.1038/s41388-023-02807-2

PubMed Abstract | Crossref Full Text | Google Scholar

116. Lang C, Yin C, Lin K, Li Y, Yang Q, Wu Z, et al. m(6) A modification of lncRNA PCAT6 promotes bone metastasis in prostate cancer through IGF2BP2-mediated IGF1R mRNA stabilization. Clin Trans Med. (2021) 11:e426. doi: 10.1002/ctm2.426

PubMed Abstract | Crossref Full Text | Google Scholar

117. Yang Z, Luo Y, Zhang F, and Ma L. Exosome-derived lncRNA A1BG-AS1 attenuates the progression of prostate cancer depending on ZC3H13-mediated m6A modification. Cell division. (2024) 19:5. doi: 10.1186/s13008-024-00110-4

PubMed Abstract | Crossref Full Text | Google Scholar

118. Guo D, Chen Y, Wang S, Yu L, Shen Y, Zhong H, et al. Exosomes from heat-stressed tumour cells inhibit tumour growth by converting regulatory T cells to Th17 cells via IL-6. Immunology. (2018) 154:132–43. doi: 10.1111/imm.12874

PubMed Abstract | Crossref Full Text | Google Scholar

119. Pan S, Zhang Y, Huang M, Deng Z, Zhang A, Pei L, et al. Urinary exosomes-based Engineered Nanovectors for Homologously Targeted Chemo-Chemodynamic Prostate Cancer Therapy via abrogating EGFR/AKT/NF-kB/IkB signaling. Biomaterials. (2021) 275:120946. doi: 10.1016/j.biomaterials.2021.120946

PubMed Abstract | Crossref Full Text | Google Scholar

120. Panigrahi GK, Praharaj PP, Peak TC, Long J, Singh R, Rhim JS, et al. Hypoxia-induced exosome secretion promotes survival of African-American and Caucasian prostate cancer cells. Sci Rep. (2018) 8:3853. doi: 10.1038/s41598-018-22068-4

PubMed Abstract | Crossref Full Text | Google Scholar

121. Lavi Arab F, Hoseinzadeh A, Hafezi F, Sadat Mohammadi F, Zeynali F, Hadad Tehran M, et al. Mesenchymal stem cell-derived exosomes for management of prostate cancer: An updated view. Int Immunopharmacol. (2024) 134:112171. doi: 10.1016/j.intimp.2024.112171

PubMed Abstract | Crossref Full Text | Google Scholar

122. Rezaeian A, Khatami F, Heidari Keshel S, Akbari MR, Mirzaei A, Gholami K, et al. The effect of mesenchymal stem cells-derived exosomes on the prostate, bladder, and renal cancer cell lines. Sci Rep. (2022) 12:20924. doi: 10.1038/s41598-022-23204-x

PubMed Abstract | Crossref Full Text | Google Scholar

123. Li C, Sun Z, Song Y, and Zhang Y. Suppressive function of bone marrow-derived mesenchymal stem cell-derived exosomal microRNA-187 in prostate cancer. Cancer Biol Ther. (2022) 23:1–14. doi: 10.1080/15384047.2022.2123675

PubMed Abstract | Crossref Full Text | Google Scholar

124. Jiang S, Chen H, He K, and Wang J. Human bone marrow mesenchymal stem cells-derived exosomes attenuated prostate cancer progression via the miR-99b-5p/IGF1R axis. Bioengineered. (2022) 13:2004–16. doi: 10.1080/21655979.2021.2009416

PubMed Abstract | Crossref Full Text | Google Scholar

125. Jiang S, Mo C, Guo S, Zhuang J, Huang B, and Mao X. Human bone marrow mesenchymal stem cells-derived microRNA-205-containing exosomes impede the progression of prostate cancer through suppression of RHPN2. J Exp Clin Cancer research: CR. (2019) 38:495. doi: 10.1186/s13046-019-1488-1

PubMed Abstract | Crossref Full Text | Google Scholar

126. Altanerova U, Babincova M, Babinec P, Benejova K, Jakubechova J, Altanerova V, et al. Human mesenchymal stem cell-derived iron oxide exosomes allow targeted ablation of tumor cells via magnetic hyperthermia. Int J Nanomedicine. (2017) 12:7923–36. doi: 10.2147/IJN.S145096

PubMed Abstract | Crossref Full Text | Google Scholar

127. Peak TC, Praharaj PP, Panigrahi GK, Doyle M, Su Y, Schlaepfer IR, et al. Exosomes secreted by placental stem cells selectively inhibit growth of aggressive prostate cancer cells. Biochem Biophys Res Commun. (2018) 499:1004–10. doi: 10.1016/j.bbrc.2018.04.038

PubMed Abstract | Crossref Full Text | Google Scholar

128. Matsuda C, Ishii K, Nakagawa Y, Shirai T, Sasaki T, Hirokawa YS, et al. Fibroblast-derived exosomal microRNA regulates NKX3–1 expression in androgen-sensitive, androgen receptor-dependent prostate cancer cells. J Cell Biochem. (2023) 124:1135–44. doi: 10.1002/jcb.30435

PubMed Abstract | Crossref Full Text | Google Scholar

129. Aalberts M, Stout TA, and Stoorvogel W. Prostasomes: extracellular vesicles from the prostate. Reprod (Cambridge England). (2014) 147:R1–14. doi: 10.1530/REP-13-0358

PubMed Abstract | Crossref Full Text | Google Scholar

130. Vlaeminck-Guillem V. Extracellular vesicles in prostate cancer carcinogenesis. Diagnosis Management Front Oncol. (2018) 8:222. doi: 10.3389/fonc.2018.00222

PubMed Abstract | Crossref Full Text | Google Scholar

131. Drake RR and Kislinger T. The proteomics of prostate cancer exosomes. Expert Rev Proteomics. (2014) 11:167–77. doi: 10.1586/14789450.2014.890894

PubMed Abstract | Crossref Full Text | Google Scholar

132. Zhu S, Ni Y, Wang Z, Zhang X, Zhang Y, Zhao F, et al. Plasma exosomal AKR1C3 mRNA expression is a predictive and prognostic biomarker in patients with metastatic castration-resistant prostate cancer. oncologist. (2022) 27:e870–7. doi: 10.1093/oncolo/oyac177

PubMed Abstract | Crossref Full Text | Google Scholar

133. Matijašević Joković S, Korać A, Kovačević S, Djordjević A, Filipović L, Dobrijević Z, et al. Exosomal prostate-specific membrane antigen (PSMA) and caveolin-1 as potential biomarkers of prostate cancer-evidence from Serbian population. Int J Mol Sci. (2024) 25. doi: 10.3390/ijms25063533

PubMed Abstract | Crossref Full Text | Google Scholar

134. Wang YH, Ji J, Wang BC, Chen H, Yang ZH, Wang K, et al. Tumor-derived exosomal long noncoding RNAs as promising diagnostic biomarkers for prostate cancer. Cell Physiol Biochem. (2018) 46:532–45. doi: 10.1159/000488620

PubMed Abstract | Crossref Full Text | Google Scholar

135. Li W, Dong Y, Wang KJ, Deng Z, Zhang W, and Shen HF. Plasma exosomal miR-125a-5p and miR-141-5p as non-invasive biomarkers for prostate cancer. Neoplasma. (2020) 67:1314–8. doi: 10.4149/neo_2020_191130N1234

PubMed Abstract | Crossref Full Text | Google Scholar

136. Evin D, Evinová A, Baranovičová E, Šarlinová M, Jurečeková J, Kaplán P, et al. Integrative metabolomic analysis of serum and selected serum exosomal microRNA in metastatic castration-resistant prostate cancer. Int J Mol Sci. (2024) 25. doi: 10.3390/ijms25052630

PubMed Abstract | Crossref Full Text | Google Scholar

137. Huang X, Yuan T, Liang M, Du M, Xia S, Dittmar R, et al. Exosomal miR-1290 and miR-375 as prognostic markers in castration-resistant prostate cancer. Eur Urol. (2015) 67:33–41. doi: 10.1016/j.eururo.2014.07.035

PubMed Abstract | Crossref Full Text | Google Scholar

138. Zhang S, Liu C, Zou X, Geng X, Zhou X, Fan X, et al. MicroRNA panel in serum reveals novel diagnostic biomarkers for prostate cancer. PeerJ. (2021) 9:e11441. doi: 10.7717/peerj.11441

PubMed Abstract | Crossref Full Text | Google Scholar

139. Del Re M, Biasco E, Crucitta S, Derosa L, Rofi E, Orlandini C, et al. The detection of androgen receptor splice variant 7 in plasma-derived exosomal RNA strongly predicts resistance to hormonal therapy in metastatic prostate cancer patients. Eur Urol. (2017) 71:680–7. doi: 10.1016/j.eururo.2016.08.012

PubMed Abstract | Crossref Full Text | Google Scholar

140. Kato T, Mizutani K, Kawakami K, Fujita Y, Ehara H, and Ito M. CD44v8–10 mRNA contained in serum exosomes as a diagnostic marker for docetaxel resistance in prostate cancer patients. Heliyon. (2020) 6:e04138. doi: 10.1016/j.heliyon.2020.e04138

PubMed Abstract | Crossref Full Text | Google Scholar

141. Li S, Zhao Y, Chen W, Yin L, Zhu J, Zhang H, et al. Exosomal ephrinA2 derived from serum as a potential biomarker for prostate cancer. J Cancer. (2018) 9:2659–65. doi: 10.7150/jca.25201

PubMed Abstract | Crossref Full Text | Google Scholar

142. Guo T, Wang Y, Jia J, Mao X, Stankiewicz E, Scandura G, et al. The Identification of Plasma Exosomal miR-423-3p as a Potential Predictive Biomarker for Prostate Cancer Castration-Resistance Development by Plasma Exosomal miRNA Sequencing. Front Cell Dev Biol. (2020) 8:602493. doi: 10.3389/fcell.2020.602493

PubMed Abstract | Crossref Full Text | Google Scholar

143. Lu Z, Hou J, Li X, Zhou J, Luo B, Liang S, et al. Exosome-derived miRNAs as potential biomarkers for prostate bone metastasis. Int J Gen Med. (2022) 15:5369–83. doi: 10.2147/IJGM.S361981

PubMed Abstract | Crossref Full Text | Google Scholar

144. Krishn SR, Singh A, Bowler N, Duffy AN, Friedman A, Fedele C, et al. Prostate cancer sheds the αvβ3 integrin in vivo through exosomes. Matrix biology: J Int Soc Matrix Biol. (2019) 77:41–57. doi: 10.1016/j.matbio.2018.08.004

PubMed Abstract | Crossref Full Text | Google Scholar

145. Joncas FH, Lucien F, Rouleau M, Morin F, Leong HS, Pouliot F, et al. Plasma extracellular vesicles as phenotypic biomarkers in prostate cancer patients. Prostate. (2019) 79:1767–76. doi: 10.1002/pros.23901

PubMed Abstract | Crossref Full Text | Google Scholar

146. Yu Q, Li P, Weng M, Wu S, Zhang Y, Chen X, et al. Nano-vesicles are a potential tool to monitor therapeutic efficacy of carbon ion radiotherapy in prostate cancer. J Biomed nanotechnology. (2018) 14:168–78. doi: 10.1166/jbn.2018.2503

PubMed Abstract | Crossref Full Text | Google Scholar

147. Øverbye A, Skotland T, Koehler CJ, Thiede B, Seierstad T, Berge V, et al. Identification of prostate cancer biomarkers in urinary exosomes. Oncotarget. (2015) 6:30357–76. doi: 10.18632/oncotarget.4851

PubMed Abstract | Crossref Full Text | Google Scholar

148. Matsuzaki K, Fujita K, Tomiyama E, Hatano K, Hayashi Y, Wang C, et al. MiR-30b-3p and miR-126-3p of urinary extracellular vesicles could be new biomarkers for prostate cancer. Trans andrology Urol. (2021) 10:1918–27. doi: 10.21037/tau-20-421

PubMed Abstract | Crossref Full Text | Google Scholar

149. Rogers CG, Yan G, Zha S, Gonzalgo ML, Isaacs WB, Luo J, et al. Prostate cancer detection on urinalysis for alpha methylacyl coenzyme a racemase protein. J Urol. (2004) 172:1501–3. doi: 10.1097/01.ju.0000137659.53129.14

PubMed Abstract | Crossref Full Text | Google Scholar

150. Jin X, Ji J, Niu D, Yang Y, Tao S, Wan L, et al. Urine exosomal AMACR is a novel biomarker for prostate cancer detection at initial biopsy. Front Oncol. (2022) 12:904315. doi: 10.3389/fonc.2022.904315

PubMed Abstract | Crossref Full Text | Google Scholar

151. Gan J, Zeng X, Wang X, Wu Y, Lei P, Wang Z, et al. Effective diagnosis of prostate cancer based on mRNAs from urinary exosomes. Front Med (Lausanne). (2022) 9:736110. doi: 10.3389/fmed.2022.736110

PubMed Abstract | Crossref Full Text | Google Scholar

152. Shin S, Park YH, Jung S-H, Jang S-H, Kim MY, Lee JY, et al. Urinary exosome microRNA signatures as a noninvasive prognostic biomarker for prostate cancer. NPJ Genomic Med. (2021) 6:45. doi: 10.1038/s41525-021-00212-w

PubMed Abstract | Crossref Full Text | Google Scholar

153. Wani S, Kaul D, Mavuduru RS, Kakkar N, and Bhatia A. Urinary-exosomal miR-2909: A novel pathognomonic trait of prostate cancer severity. J Biotechnol. (2017) 259:135–9. doi: 10.1016/j.jbiotec.2017.07.029

PubMed Abstract | Crossref Full Text | Google Scholar

154. Samsonov R, Shtam T, Burdakov V, Glotov A, Tsyrlina E, Berstein L, et al. Lectin-induced agglutination method of urinary exosomes isolation followed by mi-RNA analysis: Application for prostate cancer diagnostic. Prostate. (2016) 76:68–79. doi: 10.1002/pros.23101

PubMed Abstract | Crossref Full Text | Google Scholar

155. Lee J, Kwon MH, Kim JA, and Rhee WJ. Detection of exosome miRNAs using molecular beacons for diagnosing prostate cancer. Artif cells nanomedicine Biotechnol. (2018) 46:S52–s63. doi: 10.1080/21691401.2018.1489263

PubMed Abstract | Crossref Full Text | Google Scholar

156. Rodríguez M, Bajo-Santos C, Hessvik NP, Lorenz S, Fromm B, Berge V, et al. Identification of non-invasive miRNAs biomarkers for prostate cancer by deep sequencing analysis of urinary exosomes. Mol Cancer. (2017) 16:156. doi: 10.1186/s12943-017-0726-4

PubMed Abstract | Crossref Full Text | Google Scholar

157. Işın M, Uysaler E, Özgür E, Köseoğlu H, Şanlı Ö, Yücel ÖB, et al. Exosomal lncRNA-p21 levels may help to distinguish prostate cancer from benign disease. Front Genet. (2015) 6:168. doi: 10.3389/fgene.2015.00168

PubMed Abstract | Crossref Full Text | Google Scholar

158. Bijnsdorp IV, Geldof AA, Lavaei M, Piersma SR, van Moorselaar RJ, and Jimenez CR. Exosomal ITGA3 interferes with non-cancerous prostate cell functions and is increased in urine exosomes of metastatic prostate cancer patients. J extracellular vesicles. (2013) 2. doi: 10.3402/jev.v2i0.22097

PubMed Abstract | Crossref Full Text | Google Scholar

159. Skotland T, Ekroos K, Kauhanen D, Simolin H, Seierstad T, Berge V, et al. Molecular lipid species in urinary exosomes as potential prostate cancer biomarkers. Eur J Cancer (Oxford Engl. (2017) 1990) 70:122–32. doi: 10.1016/j.ejca.2016.10.011

PubMed Abstract | Crossref Full Text | Google Scholar

160. Barceló M, Castells M, Bassas L, Vigués F, and Larriba S. Semen miRNAs contained in exosomes as non-invasive biomarkers for prostate cancer diagnosis. Sci Rep. (2019) 9:13772. doi: 10.1038/s41598-019-50172-6

PubMed Abstract | Crossref Full Text | Google Scholar

161. Li M, Rai AJ, DeCastro GJ, Zeringer E, Barta T, Magdaleno S, et al. An optimized procedure for exosome isolation and analysis using serum samples: Application to cancer biomarker discovery, Methods (San Diego, Calif. ). (2015) 87:26–30. doi: 10.1016/j.ymeth.2015.03.009

PubMed Abstract | Crossref Full Text | Google Scholar

162. Bryant RJ, Pawlowski T, Catto JW, Marsden G, Vessella RL, Rhees B, et al. Changes in circulating microRNA levels associated with prostate cancer. Br J Cancer. (2012) 106:768–74. doi: 10.1038/bjc.2011.595

PubMed Abstract | Crossref Full Text | Google Scholar

163. Bhagirath D, Yang TL, Bucay N, Sekhon K, Majid S, Shahryari V, et al. microRNA-1246 is an exosomal biomarker for aggressive prostate cancer. Cancer Res. (2018) 78:1833–44. doi: 10.1158/0008-5472.CAN-17-2069

PubMed Abstract | Crossref Full Text | Google Scholar

164. Kohaar I, Chen Y, Banerjee S, Borbiev T, Kuo HC, Ali A, et al. A urine exosome gene expression panel distinguishes between indolent and aggressive prostate cancers at biopsy. J Urol. (2021) 205:420–5. doi: 10.1097/JU.0000000000001374

PubMed Abstract | Crossref Full Text | Google Scholar

165. Wang L, Skotland T, Berge V, Sandvig K, and Llorente A. Exosomal proteins as prostate cancer biomarkers in urine: From mass spectrometry discovery to immunoassay-based validation. Eur J Pharm Sci. (2017) 98:80–5. doi: 10.1016/j.ejps.2016.09.023

PubMed Abstract | Crossref Full Text | Google Scholar

166. Krafft C, Wilhelm K, Eremin A, Nestel S, von Bubnoff N, Schultze-Seemann W, et al. A specific spectral signature of serum and plasma-derived extracellular vesicles for cancer screening. Nanomedicine: nanotechnology biology Med. (2017) 13:835–41. doi: 10.1016/j.nano.2016.11.016

PubMed Abstract | Crossref Full Text | Google Scholar

167. Kawakami K, Fujita Y, Matsuda Y, Arai T, Horie K, Kameyama K, et al. Gamma-glutamyltransferase activity in exosomes as a potential marker for prostate cancer. BMC Cancer. (2017) 17:316. doi: 10.1186/s12885-017-3301-x

PubMed Abstract | Crossref Full Text | Google Scholar

168. Worst TS, von Hardenberg J, Gross JC, Erben P, Schnölzer M, Hausser I, et al. Database-augmented mass spectrometry analysis of exosomes identifies claudin 3 as a putative prostate cancer biomarker. Mol Cell proteomics: MCP. (2017) 16:998–1008. doi: 10.1074/mcp.M117.068577

PubMed Abstract | Crossref Full Text | Google Scholar

169. Fujita K, Kume H, Matsuzaki K, Kawashima A, Ujike T, Nagahara A, et al. Proteomic analysis of urinary extracellular vesicles from high Gleason score prostate cancer. Sci Rep. (2017) 7:42961. doi: 10.1038/srep42961

PubMed Abstract | Crossref Full Text | Google Scholar

170. Khan S, Jutzy JM, Valenzuela MM, Turay D, Aspe JR, Ashok A, et al. Plasma-derived exosomal survivin, a plausible biomarker for early detection of prostate cancer. PloS One. (2012) 7:e46737. doi: 10.1371/journal.pone.0046737

PubMed Abstract | Crossref Full Text | Google Scholar

171. Sequeiros T, Rigau M, Chiva C, Montes M, Garcia-Grau I, Garcia M, et al. Targeted proteomics in urinary extracellular vesicles identifies biomarkers for diagnosis and prognosis of prostate cancer. Oncotarget. (2017) 8:4960–76. doi: 10.18632/oncotarget.13634

PubMed Abstract | Crossref Full Text | Google Scholar

172. Li Y, You J, Zou Z, Sun G, Shi Y, Sun Y, et al. Decoding the tumor microenvironment: exosome-mediated macrophage polarization and therapeutic frontiers. Int J Biol Sci. (2025) 21:4187–214. doi: 10.7150/ijbs.114222

PubMed Abstract | Crossref Full Text | Google Scholar

173. Li MY, Liu LZ, and Dong M. Progress on pivotal role and application of exosome in lung cancer carcinogenesis. diagnosis Ther prognosis Mol Cancer. (2021) 20:22. doi: 10.1186/s12943-021-01312-y

PubMed Abstract | Crossref Full Text | Google Scholar

174. Saint-Pol J, Gosselet F, Duban-Deweer S, Pottiez G, and Karamanos Y. Targeting and crossing the blood-brain barrier with extracellular vesicles. Cells. (2020) 9. doi: 10.3390/cells9040851

PubMed Abstract | Crossref Full Text | Google Scholar

175. Zhu X, Badawi M, Pomeroy S, Sutaria DS, Xie Z, Baek A, et al. Comprehensive toxicity and immunogenicity studies reveal minimal effects in mice following sustained dosing of extracellular vesicles derived from HEK293T cells. J Extracell Vesicles. (2017) 6:1324730. doi: 10.1080/20013078.2017.1324730

PubMed Abstract | Crossref Full Text | Google Scholar

176. Batrakova EV and Kim MS. Using exosomes, naturally-equipped nanocarriers, for drug delivery. J Control Release. (2015) 219:396–405. doi: 10.1016/j.jconrel.2015.07.030

PubMed Abstract | Crossref Full Text | Google Scholar

177. Peng Q, Zhang S, Yang Q, Zhang T, Wei XQ, Jiang L, et al. Preformed albumin corona, a protective coating for nanoparticles based drug delivery system. Biomaterials. (2013) 34:8521–30. doi: 10.1016/j.biomaterials.2013.07.102

PubMed Abstract | Crossref Full Text | Google Scholar

178. Vázquez-Ríos AJ, Molina-Crespo Á, Bouzo BL, López-López R, Moreno-Bueno G, and de la Fuente M. Exosome-mimetic nanoplatforms for targeted cancer drug delivery. J Nanobiotechnology. (2019) 17:85. doi: 10.1186/s12951-019-0517-8

PubMed Abstract | Crossref Full Text | Google Scholar

179. Saari H, Lázaro-Ibáñez E, Viitala T, Vuorimaa-Laukkanen E, Siljander P, and Yliperttula M. Microvesicle- and exosome-mediated drug delivery enhances the cytotoxicity of Paclitaxel in autologous prostate cancer cells. J Control Release. (2015) 220:727–37. doi: 10.1016/j.jconrel.2015.09.031

PubMed Abstract | Crossref Full Text | Google Scholar

180. Severic M, Ma G, Pereira SGT, Ruiz A, Cheung CCL, and Al-Jamal WT. Genetically-engineered anti-PSMA exosome mimetics targeting advanced prostate cancer in vitro and in vivo. J Control Release. (2021) 330:101–10. doi: 10.1016/j.jconrel.2020.12.017

PubMed Abstract | Crossref Full Text | Google Scholar

181. Kosaka N, Iguchi H, Yoshioka Y, Hagiwara K, Takeshita F, and Ochiya T. Competitive interactions of cancer cells and normal cells via secretory microRNAs. J Biol Chem. (2012) 287:1397–405. doi: 10.1074/jbc.M111.288662

PubMed Abstract | Crossref Full Text | Google Scholar

182. Kurniawati I, Liu MC, Hsieh CL, Do AD, and Sung SY. Targeting castration-resistant prostate cancer using mesenchymal stem cell exosomes for therapeutic microRNA-let-7c delivery. Front bioscience (Landmark edition). (2022) 27:256. doi: 10.31083/j.fbl2709256

PubMed Abstract | Crossref Full Text | Google Scholar

183. Shi X, Sun J, Li H, Lin H, Xie W, Li J, et al. Antitumor efficacy of interferon-γ-modified exosomal vaccine in prostate cancer. Prostate. (2020) 80:811–23. doi: 10.1002/pros.23996

PubMed Abstract | Crossref Full Text | Google Scholar

184. Saffar A, Bahrami AR, Sh Saljooghi A, and Matin MM. ZIF-8/doxorubicin nanoparticles camouflaged with Cucurbita-derived exosomes for targeted prostate cancer therapy, Journal of materials chemistry. B. (2025) 13:5705–22. doi: 10.1039/d5tb00086f

PubMed Abstract | Crossref Full Text | Google Scholar

185. Ishizuya Y, Uemura M, Narumi R, Tomiyama E, Koh Y, Matsushita M, et al. The role of actinin-4 (ACTN4) in exosomes as a potential novel therapeutic target in castration-resistant prostate cancer. Biochem Biophys Res Commun. (2020) 523:588–94. doi: 10.1016/j.bbrc.2019.12.084

PubMed Abstract | Crossref Full Text | Google Scholar

186. Gan J, Liu S, Zhang Y, He L, Bai L, Liao R, et al. MicroRNA-375 is a therapeutic target for castration-resistant prostate cancer through the PTPN4/STAT3 axis. Exp Mol Med. (2022) 54:1290–305. doi: 10.1038/s12276-022-00837-6

PubMed Abstract | Crossref Full Text | Google Scholar

187. Lu YC, Ho CH, Hong JH, Kuo MC, Liao YA, Jaw FS, et al. NKG2A and circulating extracellular vesicles are key regulators of natural killer cell activity in prostate cancer after prostatectomy. Mol Oncol. (2023) 17:1613–27. doi: 10.1002/1878-0261.13422

PubMed Abstract | Crossref Full Text | Google Scholar

188. Peng Y, Zhao M, Hu Y, Guo H, Zhang Y, Huang Y, et al. Blockade of exosome generation by GW4869 inhibits the education of M2 macrophages in prostate cancer. BMC Immunol. (2022) 23:37. doi: 10.1186/s12865-022-00514-3

PubMed Abstract | Crossref Full Text | Google Scholar

189. Liu J, He D, Cheng L, Huang C, Zhang Y, Rao X, et al. p300/CBP inhibition enhances the efficacy of programmed death-ligand 1 blockade treatment in prostate cancer. Oncogene. (2020) 39:3939–51. doi: 10.1038/s41388-020-1270-z

PubMed Abstract | Crossref Full Text | Google Scholar

190. Fan Z, Wang Z, Zhang H, Zhang H, Zhao R, Zhu S, et al. Extracellular vesicles derived from mature dendritic cells loaded with cDC1-specific chemokine XCL1 combined with chemotherapy-induced ICD for the treatment of castration-resistant prostate cancer. Cancer Immunol Immunother. (2025) 74:242. doi: 10.1007/s00262-025-04070-8

PubMed Abstract | Crossref Full Text | Google Scholar

191. Ma X, Liu B, Fan L, Liu Y, Zhao Y, Ren T, et al. Native and Engineered Exosomes for Inflammatory Disease. Nano Research. (2023) 16:6991–7006. doi: 10.1007/s12274-022-5275-5

PubMed Abstract | Crossref Full Text | Google Scholar

192. Lin YK, Pan YF, Jiang TY, Chen YB, Shang TY, Xu MY, et al. Blocking the Sirpa-Cd47 Axis Promotes Macrophage Phagocytosis of Exosomes Derived from Visceral Adipose Tissue and Improves Inflammation and Metabolism in Mice. J Biomed Sci. (2025) 32:31. doi: 10.1186/s12929-025-01124-y

PubMed Abstract | Crossref Full Text | Google Scholar

193. Rayyan M, Zheutlin A, and Byrd JB. Clinical Research Using Extracellular Vesicles: Insights from the International Society for Extracellular Vesicles 2018 Annual Meeting. J Extracell Vesicles. (2018) 7(1):1535744. doi: 10.1080/20013078.2018.1535744

PubMed Abstract | Crossref Full Text | Google Scholar