Targeting Microvascular Pericytes in Angiogenic Vessels of Prostate Cancer
Final rept. 1 Apr 2003-31 Mar 2006
LA JOLLA INST FOR MOLECULAR MEDICINE SAN DIEGO CA
Pagination or Media Count:
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 p0.0001, and LNCaP p0.0079 xenografts. Mean MVD in TRAMP and TRAMP-C1 tumors in NG2 knockout mice were 71 p0.0006 and 63 p0.0011 lower than wild type controls, respectively. Mean LVD in TRAMP and TRAMP-C1 tumors in NG2 knockout mice were 73 p0.0003 and 84 p0.0001 lower than wild type controls, respectively. Targeting of pericyte-NG2 decreases neovascularization , lymphangiogenesis and tumor progression in prostate cancer significantly.
- Anatomy and Physiology
- Medicine and Medical Research