Targeting of pericytes diminishes neovascularization and lymphangiogenesis in prostate cancer

Prostate. 2006 Feb 15;66(3):294-304. doi: 10.1002/pros.20346.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • Antigens / immunology
  • Antigens / physiology*
  • Cell Line, Tumor
  • Corneal Neovascularization / pathology
  • Humans
  • Immunohistochemistry
  • Lymphangiogenesis
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Nude
  • Mice, Transgenic
  • Microscopy, Confocal
  • Neovascularization, Pathologic / pathology
  • Pericytes / physiology*
  • Prostatic Neoplasms / blood supply*
  • Proteoglycans / antagonists & inhibitors
  • Proteoglycans / deficiency
  • Proteoglycans / immunology
  • Proteoglycans / physiology*

Substances

  • Antibodies
  • Antigens
  • Proteoglycans
  • chondroitin sulfate proteoglycan 4