Proteolytic exposure of a cryptic site within collagen type IV is required for angiogenesis and tumor growth in vivo (vol 154, pg 1069, 2001)

被引：441

作者：

Xu, JS

Rodriguez, D

Petitclerc, E

Kim, JJ

Hangai, M

Moon, YS

Davis, GE

Brooks, PC

机构：

[1] Departments of Radiation Oncology and Cell Biology, Kaplan Cancer Center, New York University School of Medicine, New York

[2] Department of Ophthamology, Doheny Eye Institute, University of Southern California, Los Angeles

[3] Department of Pathology and Laboratory Medicine, Texas A and M University, Health Science Center, College Station

[4] Departments of Radiation Oncology and Cell Biology, Kaplan Cancer Center, New York University School of Medicine, New York, NY 10016

来源：

JOURNAL OF CELL BIOLOGY | 2001年 / 155卷 / 05期

关键词：

Angiogenesis; Cryptic sites; ECM; Migration; Tumor;

D O I：

10.1083/jcb.200103111

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：859 / 859

页数：1