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

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 angiogen...

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Detalles Bibliográficos
Autores principales: Xu, Jingsong, Rodriguez, Dorothy, Petitclerc, Eric, Kim, Jenny J., Hangai, Masanori, Yuen, S. Moon, Davis, George E., Brooks, Peter C.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2001
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196184/
https://www.ncbi.nlm.nih.gov/pubmed/11535623
http://dx.doi.org/10.1083/jcb.200103111
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author Xu, Jingsong
Rodriguez, Dorothy
Petitclerc, Eric
Kim, Jenny J.
Hangai, Masanori
Yuen, S. Moon
Davis, George E.
Brooks, Peter C.
author_facet Xu, Jingsong
Rodriguez, Dorothy
Petitclerc, Eric
Kim, Jenny J.
Hangai, Masanori
Yuen, S. Moon
Davis, George E.
Brooks, Peter C.
author_sort Xu, Jingsong
collection PubMed
description 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.
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spelling pubmed-21961842008-05-01 Proteolytic exposure of a cryptic site within collagen type IV is required for angiogenesis and tumor growth in vivo Xu, Jingsong Rodriguez, Dorothy Petitclerc, Eric Kim, Jenny J. Hangai, Masanori Yuen, S. Moon Davis, George E. Brooks, Peter C. J Cell Biol Article 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. The Rockefeller University Press 2001-09-03 /pmc/articles/PMC2196184/ /pubmed/11535623 http://dx.doi.org/10.1083/jcb.200103111 Text en Copyright © 2001, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Xu, Jingsong
Rodriguez, Dorothy
Petitclerc, Eric
Kim, Jenny J.
Hangai, Masanori
Yuen, S. Moon
Davis, George E.
Brooks, Peter C.
Proteolytic exposure of a cryptic site within collagen type IV is required for angiogenesis and tumor growth in vivo
title Proteolytic exposure of a cryptic site within collagen type IV is required for angiogenesis and tumor growth in vivo
title_full Proteolytic exposure of a cryptic site within collagen type IV is required for angiogenesis and tumor growth in vivo
title_fullStr Proteolytic exposure of a cryptic site within collagen type IV is required for angiogenesis and tumor growth in vivo
title_full_unstemmed Proteolytic exposure of a cryptic site within collagen type IV is required for angiogenesis and tumor growth in vivo
title_short Proteolytic exposure of a cryptic site within collagen type IV is required for angiogenesis and tumor growth in vivo
title_sort proteolytic exposure of a cryptic site within collagen type iv is required for angiogenesis and tumor growth in vivo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196184/
https://www.ncbi.nlm.nih.gov/pubmed/11535623
http://dx.doi.org/10.1083/jcb.200103111
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