New functions for non-collagenous domains of human collagen type IV -: Novel integrin ligands inhibiting angiogenesis and tumor growth in vivo
New functions for non-collagenous domains of human collagen type IV -: Novel integrin ligands inhibiting angiogenesis and tumor growth in vivo
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DOI：
10.1074/jbc.275.11.8051
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发表时间：
2000-03-17
影响因子：
4.8
通讯作者：
Brooks, PC
中科院分区：
文献类型：
--
作者：
Petitclerc, E;Boutaud, A;Brooks, PC
IV型胶原蛋白是血管基底层的主要成分。已鉴定出六种遗传上不同的IV型胶原蛋白链，并以组织特异性方式分布。在这里，我们定义了一个新的功能可溶性非胶原（NC 1）结构域的α 2（TV），α 3（IV）和α 6（IV）的人IV型胶原蛋白链的调节血管生成和肿瘤生长。这些NC1结构域显示通过不同的α（v）和β（1）整合素依赖性机制调节内皮细胞粘附和迁移。全身施用重组α 2（IV）、α 3（IV）和α 6（IV）NC1结构域有效地抑制血管生成和肿瘤生长，而α 1（IV）、α 4（IV）和α 5（IV）显示出几乎没有效果。这些研究结果表明，特定的NC1结构域的IV型胶原蛋白可能代表一类重要的新的血管生成抑制剂。
Collagen type IV is a major component of the basal lamina of blood vessels. Six genetically distinct collagen type IV chains have been identified and are distributed in a tissue-specific manner. Here we define a novel function for soluble non-collagenous (NC1) domains of the alpha 2(TV), alpha 3(IV), and alpha 6(IV) chains of human collagen type IV in the regulation of angiogenesis and tumor growth. These NC1 domains were shown to regulate endothelial cell adhesion and migration by distinct alpha(v) and beta(1) integrin-dependent mechanisms. Systemic administration of recombinant alpha 2(IV), alpha 3(IV), and alpha 6(IV) NC1 domains potently inhibit angiogenesis and tumor growth, whereas alpha 1(TV), alpha 4(TV), and alpha 5(IV) showed little if any effect. These findings suggest that specific NC1 domains of collagen type IV may represent an important new class of angiogenesis inhibitors.