Proteolytic exposure of a cryptic site within collagen type IV is required for angiogenesis and tumor growth in vivo.
Proteolytic exposure of a cryptic site within collagen type IV is required for angiogenesis and tumor growth in vivo.
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DOI：
10.1083/jcb.200103111
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发表时间：
2001-09-03
期刊：
影响因子：
--
通讯作者：
Brooks PC
中科院分区：
文献类型：
--
作者：
Xu J;Rodriguez D;Petitclerc E;Kim JJ;Hangai M;Moon YS;Davis GE;Brooks PC
有证据表明，IV型胶原蛋白的蛋白水解裂解导致隐藏在其三螺旋结构内的功能重要的隐蔽位点暴露。该隐蔽部位的暴露与血管生成相关，但与静止血管无关，并且是体内血管生成所需的。HUIV26表位的暴露与α1β1整联蛋白结合的丧失和αvβ3结合的获得相关。针对该位点的单克隆抗体（HUIV26）破坏整合素依赖性内皮细胞相互作用，并有效抑制血管生成和肿瘤生长。总之，这些研究提出了一种新的机制，蛋白水解有助于血管生成暴露内基质固定的IV型胶原蛋白的隐藏的调节元件。
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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影响因子：
64.5
作者：
Hiraoka, N;Allen, E;Weiss, SJ
通讯作者：
Weiss, SJ
影响因子：
15.9
作者：
Stetler-Stevenson, WG
通讯作者：
Stetler-Stevenson, WG
影响因子：
64.5
作者：
BROOKS, PC;MONTGOMERY, AMP;CHERESH, DA
通讯作者：
CHERESH, DA
DOI：
10.1073/pnas.93.18.9764
发表时间：
1996-09-03
影响因子：
11.1
作者：
Friedlander, M;Theesfeld, CL;Cheresh, DA
通讯作者：
Cheresh, DA
影响因子：
64.5
作者：
Brooks, PC;Stromblad, S;Cheresh, DA
通讯作者：
Cheresh, DA