Nov 19, 2002

Endorepellin, a novel inhibitor of angiogenesis derived from the C terminus of perlecan

The Journal of Biological Chemistry
M MongiatR V Iozzo

Abstract

Perlecan, a ubiquitous basement membrane heparan sulfate proteoglycan, plays key roles in blood vessel growth and structural integrity. We discovered that the C terminus of perlecan potently inhibited four aspects of angiogenesis: endothelial cell migration, collagen-induced endothelial tube morphogenesis, and blood vessel growth in the chorioallantoic membrane and in Matrigel plug assays. The C terminus of perlecan was active at nanomolar concentrations and blocked endothelial cell adhesion to fibronectin and type I collagen, without directly binding to either protein; henceforth we have named it "endorepellin." We also found that endothelial cells possess a significant number of high affinity (K(d) of 11 nm) binding sites for endorepellin and that endorepellin binds endostatin and counteracts its anti-angiogenic effects. Thus, endorepellin represents a novel anti-angiogenic product, which may retard tumor neovascularization and hence tumor growth in vivo.

Mentioned in this Paper

Angiogenic Process
Proteins, Recombinant DNA
Blood Vessel
Recombinant Human Endostatin
Tumor Angiogenesis
Zyderm
Endothelium, Vascular
Pathologic Neovascularization
Peptide Fragments
Oligonucleotide Primers

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