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© The Rockefeller University Press, 0021-9525/2001/9/1069 $5.00
The Journal of Cell Biology, Volume 154, Number 5, September 3, 2001 1069-1080

Proteolytic exposure of a cryptic site within collagen type IV is required for angiogenesis and tumor growth in vivo

¹ Departments of Radiation Oncology and Cell Biology, Kaplan Cancer Center, New York University School of Medicine, New York, NY 10016
² Department of Ophthamology, Doheny Eye Institute, University of Southern California, Los Angeles, CA 90033
³ Department of Pathology and Laboratory Medicine, Texas A & M University Health Science Center, College Station, TX 77843

Address correspondence to Peter C. Brooks, Departments of Radiation Oncology and Cell Biology, Kaplan Cancer Center, Rusk Building Room 806, New York University School of Medicine, 400 East 34th St., New York, NY 10016. Tel.: (212) 263-3021. Fax: (212) 263-3018. E-mail: peter.brooks{at}med.nyu.edu

Evidence is provided that proteolytic cleavage of collagen type IV results in the exposure of a functionally important cryptic site hidden within its triple helical structure. Exposure of this cryptic site was associated with angiogenic, but not quiescent, blood vessels and was required for angiogenesis in vivo. Exposure of the HUIV26 epitope was associated with a loss of 1ß1 integrin binding and the gain of vß3 binding. A monoclonal antibody (HUIV26) directed to this site disrupts integrin-dependent endothelial cell interactions and potently inhibits angiogenesis and tumor growth. Together, these studies suggest a novel mechanism by which proteolysis contributes to angiogenesis by exposing hidden regulatory elements within matrix-immobilized collagen type IV.

Key Words: angiogenesis; ECM; cryptic sites; tumor; migration

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