SPP1

Secreted phosphoprotein 1 (SPP1), commonly termed osteopontin (OPN), is a multifunctional extracellular matrix glycoprotein involved in cell-matrix interactions and immune modulation. It binds integrin receptors (αvβ3, αvβ5) and CD44 variants to activate downstream signaling pathways including PI3K/AKT, MAPK, and NF-κB, regulating processes such as cell adhesion, chemotaxis, and survival. OPN is implicated in biomineralization, tissue remodeling, and inflammatory responses. Its overexpression correlates with tumor progression through epithelial-mesenchymal transition (EMT) promotion and angiogenesis. Key pathways associated with OPN encompass the TGF-β/Smad axis and Wnt/β-catenin cascades, which intersect with its role in fibrosis and metastatic niche formation.
Elevated OPN levels are biomarkers for cancers (breast, hepatocellular), autoimmune disorders (multiple sclerosis), and cardiovascular diseases (atherosclerosis). Therapeutic strategies targeting OPN include neutralizing antibodies (e.g., huOPN-305), small-molecule inhibitors disrupting integrin-OPN binding, and siRNA-based silencing. A phase I trial of the anti-OPN antibody ASK8007 demonstrated reduced tumor growth in triple-negative breast cancer models. Additionally, OPN blockade synergizes with immune checkpoint inhibitors by attenuating immunosuppressive tumor microenvironments. Ongoing research explores its diagnostic potential in non-alcoholic steatohepatitis (NASH) and as a therapeutic target for osteolytic bone metastases.