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. Here, SPON2 is linked to neoplasm.