Abstract

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 α1β1 integrin binding and the gain of αvβ3 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.

Keywords

BiologyAngiogenesisIn vivoCell biologyCancer researchGenetics

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Year
2001
Type
article
Volume
154
Issue
5
Pages
1069-1080
Citations
477
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Jingsong Xu, Dorothy Rodriguez, Éric Petitclerc et al. (2001). Proteolytic exposure of a cryptic site within collagen type IV is required for angiogenesis and tumor growth in vivo. The Journal of Cell Biology , 154 (5) , 1069-1080. https://doi.org/10.1083/jcb.200103111

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DOI
10.1083/jcb.200103111