The Multifaceted Role of Osteopontin in Modulating the Tumor Microenvironment

Osteopontin (OPN), a key structural protein in the extracellular matrix, plays a pivotal role in regulating the local tumor microenvironment and systemic immunity during cancer progression. Recognizing that tumor cells do not exist in isolation but rather interact with a multitude of stromal components that significantly influence patient outcomes and therapy responses, this review focuses on the role of OPN in nontumor cells in the context of solid cancers and the associated phenotypic and mechanistic insights. We explore how OPN influences the behavior of various innate and adaptive immune cells, including NK cells, neutrophils, macrophages, dendritic cells, myeloid-derived suppressor cells, B cells, and T cells, as well as structural stromal cells such as fibroblasts, endothelial cells, and adipocytes. The review highlights the roles of OPN in modulating these stromal cells and their multiaxial influence on tumorigenesis and metastasis. These complex interplays offer insights into potential diagnostic and therapeutic strategies around OPN/stromal-mediated pathways in cancer progression and recurrence.