The angiogenic response is dictated by beta3 integrin on bone marrow-derived cells.
The angiogenic response is dictated by beta3 integrin on bone marrow-derived cells.
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DOI：
10.1083/jcb.200802179
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发表时间：
2008-12-15
期刊：
影响因子：
--
通讯作者：
Byzova TV
中科院分区：
文献类型：
--
作者：
Feng W;McCabe NP;Mahabeleshwar GH;Somanath PR;Phillips DR;Byzova TV
血管生成取决于多种细胞类型的协调作用。由这些细胞表达的关键粘附分子是αvβ3整联蛋白。在这里，我们表明，虽然这种受体存在于大多数血管和血细胞，在肿瘤和伤口血管生成的关键调节功能是由β3整合素对骨髓来源的细胞（BMDCs）招募到新血管形成的网站。使用表达功能发育不良的β3整合素的敲入小鼠，我们表明骨髓移植通过使BMDC募集正常化来挽救这些小鼠中受损的血管生成。我们证明αvβ3整合素通过介导细胞粘附和BMDC通过内皮单层的迁移而不是它们从骨龛的释放来增强BMDC在血管生成部位的募集和保留。因此，β3整联蛋白具有通过调节BMDC募集到经历病理性和适应性血管生成的位点来控制诸如肿瘤生长和伤口愈合的过程的潜力。
Angiogenesis is dependent on the coordinated action of numerous cell types. A key adhesion molecule expressed by these cells is the αvβ3 integrin. Here, we show that although this receptor is present on most vascular and blood cells, the key regulatory function in tumor and wound angiogenesis is performed by β3 integrin on bone marrow–derived cells (BMDCs) recruited to sites of neovascularization. Using knockin mice expressing functionally stunted β3 integrin, we show that bone marrow transplantation rescues impaired angiogenesis in these mice by normalizing BMDC recruitment. We demonstrate that αvβ3 integrin enhances BMDC recruitment and retention at angiogenic sites by mediating cellular adhesion and transmigration of BMDCs through the endothelial monolayer but not their release from the bone niche. Thus, β3 integrin has the potential to control processes such as tumor growth and wound healing by regulating BMDC recruitment to sites undergoing pathological and adaptive angiogenesis.
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