Targeting of pericytes diminishes neovascularization and lymphangiogenesis in prostate cancer.

BACKGROUND

The walls of capillaries in prostate cancer are composed of endothelial cells, and pericytes. NG2 is a transmembrane proteoglycan on nascent pericytes with a functional role in neovascularization.

METHODS

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).

RESULTS

NG2 neutralizing antibody decreased corneal neovascularization in PC3 (P<0.0001), and LNCaP (P=0.0079) xenografts. Mean MVD in TRAMP and TRAMP-C1 tumors in NG2 knockout mice were 71% (P=0.0006) and 63% (P=0.0011) lower than wild type controls, respectively. Mean LVD in TRAMP and TRAMP-C1 tumors in NG2 knockout mice were 73% (P=0.0003) and 84% (P<0.0001) lower than wild type controls, respectively.

CONCLUSIONS

Targeting of pericyte-NG2 decreases neovascularization and lymphangiogenesis in prostate cancer significantly.