Targeting Microvascular Pericytes in Angiogenic Vessels of Prostate Cancer

摘要

The walls of neovascular capillaries in prostate cancer are composed of endothelial cells and pericytes. Pericytes of postnatal pathological neovascularization have dual origin: They derive from bone marrow progenitors (vasculogenesis),or by sprouting from pre-existing vessels (angiogenesis). NG2+ nascent pericytes promote neovascularization and increase interstitial fluid pressure in tumors. The aims of this investigation are to determine whether therapeutic interference with pericyte-NG2 proteoglycan decreases prostate cancer neovascularization, and controls tumor growth. The anti-angiogenic effect of hydron pellets containing NG2 neutralizing antibody was quantified in intracorneal PC-3 and LNCaP xenografts. TRAMP and TRAMP-C1 tumors grafted in NG2 knockout mice represented intrinsic pericyte targeting. TRAMP and TRAMP-C1 grafts were analyzed with confocal microscope for microvascular density (MVD) and lymphatic vascular density (LVD). NG2 neutralizing antibody decreased corneal neovascularization in PC3.