Mechanistically, SPON2 enhances interleukin 10 (IL10), C-C motif chemokine ligand 2 (CCL2), and colony stimulating factor 1 (CSF1) secretion, drives M2 macrophage polarization, and activates the NF-κB/VEGF signaling axis to facilitate EMT and tumor progression. The gene discussed is IL10; the disease is neoplasm.