PDGF and vessel maturation

Abstract

Pericytes are smooth muscle-like cells found in close contact with the endothelium in capillaries, where they regulate the morphology and function of the vessels. During vessel formation, platelet-derived growth factor-BB (PDGF-BB) is required for the recruitment and differentiation of pericytes. Tumor vessels display abnormal morphology and increased endothelial proliferation, resulting in leaky, tortuous vessels that are often poorly perfused. These vessels typically display decreased pericyte density, and the tumor-associated pericytes often express abnormal markers and show abnormal morphology. Anti-angiogenic therapy targeting pro-angiogenic growth factor pathways has been applied to a broad range of solid tumors with varying results. Studies utilizing mouse models indicate that the presence of pericytes protect endothelial cells against inhibition of vascular endothelial growth factor (VEGF) signaling. Simultaneous inhibition of PDGF receptors on pericytes therefore improves the effect of VEGF inhibitors on endothelial cells and enhances anti-angiogenic therapy.