Osteopontin (OPN), a member of the small integrin binding ligand n-linked glycoprotein (SIBLING) family, plays a crucial role in the extracellular matrix (ECM) as an aspartic acid-rich, glycosylated phospho-sialoprotein with chemokine-like properties. It exists in five splice variants: OPN-a, OPN-b, OPN-c, OPN-4, and OPN-5, which exhibit differential expression and impact based on cancer type. OPN is intrinsically linked to cancer pathophysiological phenomena like tumor progression, metastasis, angiogenesis, stromal remodeling, immunomodulation, and metabolic reprogramming. By engaging with integrins and CD44, OPN activates oncogenic signaling pathways. Recent studies have highlighted the abundance of SPP1-positive macrophages within the tumor core that interact to foster an immunosuppressive tumor immune microenvironment (TIME). Other research indicates how the SPP1 and CXCL9 ratio influences macrophage polarization towards pro or anti-tumor states, alongside effects on fibroblast transformation, T-cell suppression, metabolic shifts, and autophagy processes.
OPN's discovery as an immobilized ECM protein in human bone expanded to recognize its soluble cytokine functions in body fluids, linking it to a spectrum of physiological and pathological events. A substantial body of research documents OPN's role in several cancers including breast, hepatocellular carcinoma, prostate, lung, gastric, and pancreatic ductal carcinoma. Single-cell and transcriptomic studies further underscore OPN-associated macrophage presence and their interaction with tumor core components. Despite advances in understanding OPN's basic biology, further exploration for translational applications targeting OPN or its splice variants is warranted. Potential strategies include dual inhibitors targeting OPN and integrins, immune checkpoint inhibitor roles, small molecule or phytochemical approaches, and generating specific antibodies against OPN proteins.
This Research Topic aims to elucidate OPN's complex involvement in cancer and advance its translational potential. To gather further insights within these boundaries, we welcome articles addressing, but not limited to, the following themes:
- OPN role in tumor microenvironment remodeling
- OPN-mediated immune modulation
- Novel signaling pathways activated by OPN
- OPN's impact on metabolic reprogramming
- Macrophage plasticity in response to OPN
- OPN-mediated tumor progression, metastasis, and angiogenesis
- Therapeutics targeting OPN
- OPN as an immune checkpoint and immunotherapy target
- OPN's interaction with exosomes
- OPN's role in cancer stem cell maintenance and dormancy
- OPN-induced drug resistance
- Additional areas exploring osteopontin's role in cancer
We welcome Original Research, Review, Mini Review, and Perspective articles exploring these themes.
Keywords: Osteopontin (OPN), Tumor microenvironment, Immunomodulation, Cancer progression, Therapeutic strategies
Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
