SPON2 facilitates osteosarcoma development by inducing M2 macrophage polarization through activation of the NF-κB/VEGF signaling axis.

ABSTRACT: Osteosarcoma (OS) is an aggressive bone tumor with poor prognosis, particularly in metastatic cases. Here, we identify spondin 2 (SPON2) as a key driver of OS progression. SPON2 is significantly upregulated in OS tissues and cell lines and correlates with shorter patient survival. Functional assays show that SPON2 promotes OS cell proliferation, migration, invasion, and angiogenesis by enhancing the secretion of IL10, CCL2, and CSF1, which leads to M2 macrophage polarization and an immunosuppressive tumor microenvironment. In vitro, SPON2 knockdown reduces M2 macrophage markers and attenuates EMT phenotypes, as evidenced by decreased mesenchymal markers and preserved epithelial characteristics. Mechanistically, SPON2 activates the NF-κB/VEGF signaling axis to drive both macrophage polariza

SUBMITTER: Lu X 

PROVIDER: S-EPMC12307574 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature