Figure 1.

The proliferation and differentiation of perivascular (p) MSCs in cancer can give rise either to pericytes, perivascular fibroblasts, cancer-associated fibroblasts, as well as cancer stem cells. The vascular unit is formed by endothelial cells (CD93+), peridentothelial pericytes (PCs, CD248^high) embedded into the extracellular matrix (ECM, e.g., multimerin-2) of the basement membrane, and perivascular mesenchymal stem cells (pMSCs CD248^low/CD90+). Single-cell RNA profiling experiments have indicated that PCs (e.g., in the CNS) may give rise to subsets of pMSCs, which can proliferate, particularly in response to PDGF, and differentiate into either fibroblasts subsets (ECM^high or VEGF^high), cancer-associated fibroblasts (CAFs to support tumor growth), or cancer stem cells (CSCs), as recently evidenced in glioblastoma [63,73]. Fibroblasts stimulated by TGF-β1 may give rise to myofibroblasts (Smooth Muscle cell Actin/SMA^high/ECM^high). TAMs: tumor-associated macrophages. (Figure designed by BioRender).