Histidine-rich glycoprotein inhibits the antiangiogenic effect of thrombospondin-1. J Clin Invest 2001 Jan;107(1):45-52
Date
01/03/2001Pubmed ID
11134179Pubmed Central ID
PMC198540DOI
10.1172/JCI9061Scopus ID
2-s2.0-0035171206 (requires institutional sign-in at Scopus site) 104 CitationsAbstract
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.
Author List
Simantov R, Febbraio M, Crombie R, Asch AS, Nachman RL, Silverstein RLAuthor
Roy L. Silverstein MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceBinding Sites
Breast Neoplasms
Cell Movement
Cells, Cultured
Endothelium, Vascular
Female
Glycoproteins
Humans
In Vitro Techniques
Models, Biological
Molecular Sequence Data
Neovascularization, Pathologic
Neovascularization, Physiologic
Proteins
Repetitive Sequences, Amino Acid
Sequence Homology, Amino Acid
Thrombospondin 1
