Histidine-rich glycoprotein inhibits the antiangiogenic effect of thrombospondin-1. Academic Article uri icon

Overview

abstract

  • Angiogenesis is critical for the growth and proliferation of tumors as well as for normal development. We now describe a novel role for histidine-rich glycoprotein (HRGP) in the modulation of angiogenesis. HRGP is a plasma protein that circulates in relatively high concentrations (1.5 microM), but has no known function in vivo. We have shown previously that HRGP binds with high affinity to thrombospondin-1 (TSP-1), a homotrimeric glycoprotein that is a potent inhibitor of angiogenesis. The antiangiogenic activity of TSP-1 is mediated by the binding of properdin-like type I repeats to the receptor CD36. We found that binding of HRGP to TSP-1 was similarly mediated by TSP type I repeats. HRGP colocalized with TSP-1 in the stroma of human breast cancer specimens, and this interaction masked the antiangiogenic epitope of TSP-1. In assays performed in vitro of endothelial cell migration and tube formation, and in vivo corneal angiogenesis assays, HRGP inhibited the antiangiogenic effect of TSP-1. These studies suggest that HRGP can modulate the antiangiogenic activity of TSP-1, and identify a potential mechanism of resistance to the antiangiogenic effect of TSP-1.

publication date

  • January 1, 2001

Research

keywords

  • Glycoproteins
  • Neovascularization, Physiologic
  • Proteins
  • Thrombospondin 1

Identity

PubMed Central ID

  • PMC198540

Scopus Document Identifier

  • 0035171206

Digital Object Identifier (DOI)

  • 10.1172/JCI9061

PubMed ID

  • 11134179

Additional Document Info

volume

  • 107

issue

  • 1