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Histidine-rich glycoprotein inhibits the antiangiogenic effect of thrombospondin-1
Ronit Simantov, … , Ralph L. Nachman, Roy L. Silverstein
Ronit Simantov, … , Ralph L. Nachman, Roy L. Silverstein
Published January 1, 2001
Citation Information: J Clin Invest. 2001;107(1):45-52. https://doi.org/10.1172/JCI9061.
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Article

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

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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 μM), 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.

Authors

Ronit Simantov, Maria Febbraio, René Crombie, Adam S. Asch, Ralph L. Nachman, Roy L. Silverstein

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Figure 9

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Model: HRGP inhibits the antiangiogenic effect of TSP-1. Angiogenesis in...
Model: HRGP inhibits the antiangiogenic effect of TSP-1. Angiogenesis induced by bFGF (left) is inhibited by TSP-1 through the interaction of the TSP type I repeat with the CLESH-1 domain of the signaling receptor CD36 (center). HRGP, which also contains the CLESH-1 motif, binds TSP-1, inhibiting the interaction of TSP-1 with CD36, thereby inhibiting the antiangiogenic effect of TSP-1 (right).

Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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