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.
Ozerdem
Ugur
U
La Jolla Institute for Molecular Medicine, San Diego, California 92121, USA. ozerdem@ljimm.org
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000941:Antigens / Q000276:immunology / Q000502:physiology*; D045744:Cell Line, Tumor; D016510:Corneal Neovascularization / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D042583:Lymphangiogenesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009389:Neovascularization, Pathologic / Q000473:pathology; D020286:Pericytes / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000098:blood supply*; D011509:Proteoglycans / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000276:immunology / Q000502:physiology*; D000099216:Chondroitin Sulfate Proteoglycan 4
D000906:Antibodies; D000941:Antigens; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4