1. Academic Validation
  2. Histidine-rich glycoprotein inhibits the antiangiogenic effect of thrombospondin-1

Histidine-rich glycoprotein inhibits the antiangiogenic effect of thrombospondin-1

  • J Clin Invest. 2001 Jan;107(1):45-52. doi: 10.1172/JCI9061.
R Simantov 1 M Febbraio R Crombie A S Asch R L Nachman R L Silverstein
Affiliations

Affiliation

  • 1 Division of Hematology-Oncology, Department of Medicine, Weill Medical College of Cornell University, New York, New York 10021, USA. rsimant@mail.med.cornell.edu
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.

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