REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicThe Role of Immune and Stromal Mediators in the Formation of Pre-Metastatic and Metastatic Niches: The Gateway to MetastasisView all 3 articles
Platelets and platelet-derived extracellular vesicles: their role in lung cancer dissemination and premetastatic niche formation
Provisionally accepted
- 1National Cancer Institute Foundation (IRCCS), Milan, Italy
- 2Sahlgrenska Centrum for Cancerforskning, Gothenburg, Sweden
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Metastasis, the primary cause of cancer-related mortality, is sustained by complex interactions between tumor cells and host-derived factors. Extracellular vesicles (EVs), membrane-bound particles that mediate intercellular communication, have emerged as critical regulators of this process. Among them, platelet-derived EVs extracellular vesicles (PEVs) represent the most abundant EV population in circulation and extend the multifaceted influence of platelets in cancer progression. Platelets actively contribute to metastasis by shielding circulating tumor cells (CTCs) from immune surveillance, promoting vascular remodelling, facilitating extravasation, and releasing soluble factors that shape the premetastatic niche (PMN). Pplatelet-derived extracellular vesicles further potentiate these processes by delivering a heterogeneous cargo of proteins, nucleic acids, and lipids to endothelial, stromal, and immune cells, thereby promoting angiogenesis, extracellular matrix remodelling, immune suppression, and organ-specific metastatic colonization. PEVs further amplify these effects by transferring a heterogeneous cargo of proteins, nucleic acids, and lipids to endothelial, stromal, and immune cells, thereby promoting angiogenesis, extracellular matrix (ECM) remodelling, immune suppression, and organ-specific colonization. This review summarizes current evidence on the cooperative roles of platelets and platelet-derived extracellular vesicles in metastatic dissemination, with particular emphasis on their contribution to lung premetastatic niche formation and their emerging translational potential in oncology.This review synthesizes current evidence on the cooperative roles of platelets and PEVs in metastatic dissemination, with emphasis on their contribution to PMN formation in the lungs, liver, bone, and brain. Moreover, it discusses the translational potential of PEVs in oncology.
Keywords: lung cancer, Extracellular vesicle (EV), Platelet, metastasis, microRNA
Received: 12 Sep 2025; Accepted: 11 Nov 2025.
Copyright: © 2025 Locatelli, Ferrario, Fortunato, Ghidotti and Crescitelli. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Orazio Fortunato, orazio.fortunato@istitutotumori.mi.it
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