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Osteopontin (OPN) is a multifunctional protein that plays diverse roles in physiological and pathological processes. It acts as a molecular bridge between cells and their extracellular environment, interacting with various cell surface receptors and participating in cellular processes such as adhesion, migration, inflammation, and signaling pathways. OPN exists in different isoforms and undergoes post-translational modifications that can alter its properties and functions. In physiological contexts, OPN contributes to tissue maintenance, wound healing, immune system regulation, and stress response mechanisms. However, it is also involved in the pathogenesis of conditions such as atherosclerosis, cancer, autoimmune disorders, chronic inflammation, and sepsis. OPN can serve as a diagnostic and prognostic biomarker for these disorders, and certain OPN gene polymorphisms are associated with disease susceptibility or progression. This Special Issue of Biomedicines explores the multifaceted roles of OPN in health and disease through eight papers, including studies on its role as a biomarker for glomerulopathies, coronary artery disease, melanoma metastasis, and dental biofilm formation. The issue also includes reviews on OPN's involvement in the central nervous system, thyroid cancer, and infectious diseases. Overall, OPN plays a central role in various biological activities and continues to be a subject of ongoing research to further understand its significance in different contexts. [Extracted from the article]

This editorial from the journal Biomedicines titled "Osteopontin: A Versatile Biomarker—Insights and Innovations from Three Decades of Research" discusses the significance of osteopontin (OPN) as a biomarker in different diseases and its potential as a diagnostic and prognostic tool. The editorial includes twelve papers that explore OPN's mechanisms of action in various pathological conditions, such as Hodgkin's lymphoma, multiple sclerosis, acute pancreatitis, and melanoma. It also highlights the role of OPN in chronic subdural hematoma and its potential as a therapeutic target. The article provides a comprehensive overview of the current understanding of OPN and its implications in different diseases. The authors emphasize the need for further research on OPN as a biomarker in cancer, autoimmune diseases, and inflammatory diseases. [Extracted from the article]

Recently, we demonstrated that inducible T-cell costimulator (ICOS) shares its unique ligand (ICOSL) with osteopontin (OPN), and OPN/ICOSL binding promotes tumor metastasis and angiogenesis in the 4T1 breast cancer model. Literature showed that OPN promotes melanoma metastasis by suppressing T-cell activation and recruiting myeloid suppressor cells (MDSC). On the opposite, ICOS/ICOSL interaction usually sustains an antitumor response. Here, we engineered murine B16F10 melanoma cells, by transfecting or silencing ICOSL. In vitro data showed that loss of ICOSL favors anchorage-independent growth and induces more metastases in vivo, compared to ICOSL expressing cells. To dissect individual roles of the three molecules, we compared data from C57BL/6 with those from OPN-KO, ICOS-KO, and ICOSL-KO mice, missing one partner at a time. We found that OPN produced by the tumor microenvironment (TME) favors the metastasis by interacting with stromal ICOSL. This activity is dominantly inhibited by ICOS expressed on TME by promoting Treg expansion. Importantly, we also show that OPN and ICOSL highly interact in human melanoma metastases compared to primary tumors. Interfering with this binding may be explored in immunotherapy either for nonresponding or patients resistant to conventional therapies. [ABSTRACT FROM AUTHOR]