Fig. 8: Proposed Working Model.

SPON2 is significantly upregulated in OS, driving tumor proliferation and metastasis. Mechanistically, SPON2 promotes M2 macrophage polarization by activating the NF-κB/VEGF signaling axis and modulating cytokine secretion, including IL10, CCL2, and CSF1, thereby fostering an immunosuppressive tumor microenvironment that facilitates OS progression.