Endorepellin, a novel inhibitor of angiogenesis derived from the C terminus of perlecan.
Article Details
- CitationCopy to clipboard
Mongiat M, Sweeney SM, San Antonio JD, Fu J, Iozzo RV
Endorepellin, a novel inhibitor of angiogenesis derived from the C terminus of perlecan.
J Biol Chem. 2003 Feb 7;278(6):4238-49. Epub 2002 Nov 14.
- PubMed ID
- 12435733 [ View in PubMed]
- 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.