Canstatin, a novel matrix-derived inhibitor of angiogenesis and tumor growth. J Biol Chem 2000 Jan 14;275(2):1209-15
Date
01/08/2000Pubmed ID
10625665DOI
10.1074/jbc.275.2.1209Scopus ID
2-s2.0-0033979905 (requires institutional sign-in at Scopus site) 415 CitationsAbstract
We isolated and identified an endogenous 24-kDa human basement membrane-derived inhibitor of angiogenesis and tumor growth, termed canstatin. Canstatin, a fragment of the alpha2 chain of type IV collagen, was produced as a recombinant molecule in Escherichia coli and 293 embryonic kidneys cells. Canstatin significantly inhibited human endothelial cell migration and murine endothelial cell tube formation. Additionally, canstatin potently inhibited 10% fetal bovine serum-stimulated endothelial cell proliferation and induced apoptosis, with no inhibition of proliferation or apoptosis observed on non-endothelial cells. Inhibition of endothelial proliferation was not concomitant with a change in extracellular signal-regulated kinase activation. We demonstrate that apoptosis induced by canstatin was associated with a down-regulation of the anti-apoptotic protein, FLIP. Canstatin also suppressed in vivo growth of large and small size tumors in two human xenograft mouse models with histology revealing decreased CD31-positive vasculature. Collectively, these results suggest that canstatin is a powerful therapeutic molecule for suppressing angiogenesis.
Author List
Kamphaus GD, Colorado PC, Panka DJ, Hopfer H, Ramchandran R, Torre A, Maeshima Y, Mier JW, Sukhatme VP, Kalluri RAuthor
Ramani Ramchandran PhD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Angiogenesis InhibitorsAnimals
Apoptosis
Cattle
Cell Division
Cell Line
Cell Movement
Cells, Cultured
Cloning, Molecular
Collagen
Endothelium, Vascular
Escherichia coli
Humans
Mice
Neovascularization, Physiologic
Pulmonary Artery
Recombinant Proteins
Transfection
