Within perivascular corridors, infiltrating monocyte-derived and border-associated/perivascular macrophages are the dominant SPP1 producers (microglia contribute less); SPP1—both secreted and matrix-bound (ECM-tethered)—engages CD44 on mesenchymal-shifted glioma cells and endothelial/pericyte compartments; CD44 isoform usage (CD44s with context-dependent CD44v6/v10) and integrin co-receptors (e.g., αvβ3/αvβ5) tune adhesion/angiogenic outputs that reinforce mesenchymal programs (62, 63). Here, SPP1 is linked to glioma.