Specifically, their pro-metastatic capacity is driven by the enrichment of the SPP1+ macrophage subset, which enhances tumor cell invasiveness and remodels the ECM through secretion of osteopontin (SPP1) and CXCL12, thereby activating pathways such as the SPP1-CD44/PTGER4 signaling axis (73). This evidence concerns the gene CXCL12 and neoplasm.