SPP1 作为肿瘤微环境中的核心介质：协调细胞间通讯、免疫逃逸与治疗耐药

Secreted phosphoprotein-1 (SPP1) is a multifaceted glycoprotein that extends beyond its role as a mere component of the extracellular matrix, functioning instead as a pivotal signaling hub within the tumor microenvironment (TME). This review synthesizes current evidence regarding how SPP1 orchestrates a complex cellular network by mediating bidirectional crosstalk between cancer cells and key stromal components including cancer-associated fibroblasts, tumor-associated macrophages, endothelial cells, and lymphocytes.

We elucidate how these interactions drive TME reprogramming, facilitating processes such as extracellular matrix remodeling, angiogenesis, immune evasion, and the establishment of therapeutic resistance to both chemotherapy and immunotherapy.

Furthermore, we assess emerging therapeutic strategies targeting SPP1 such as aptamers and antibodies, highlighting their preclinical efficacy alongside the translational challenges that must be addressed. Ultimately, targeting the SPP1-mediated network represents a promising approach for dismantling the pro-tumorigenic TME and enhancing cancer treatment outcomes.