Fibroblast migration on fibronectin requires three distinct functional domains
Fibroblast migration on fibronectin requires three distinct functional domains
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DOI：
10.1046/j.1523-1747.2003.12484.x
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发表时间：
2003-10-01
影响因子：
6.5
通讯作者：
Schwarzbauer, JE
中科院分区：
文献类型：
--
作者：
Clark, RAF;An, JQ;Schwarzbauer, JE
间充质细胞的运动通常受到限制;然而，纤连蛋白可以在胚胎发生、形态发生和伤口愈合期间为基质细胞迁移提供途径。细胞可以通过整合素和非整合素受体粘附到纤连蛋白上，这些受体结合多个独特的肽序列。合成肽和重组蛋白被用来描绘人成纤维细胞迁移所需的功能域纤连蛋白。第9和第10纤连蛋白III型重复，其中含有RGD和PHSRN协同细胞附着序列，支持几乎最大的成纤维细胞附着，但不迁移的原代真皮成纤维细胞。肝素结构域和IIICS区域内的特定序列也是迁移所必需的。这些研究结果预测和额外的数据证实了合作的必要性，多个整合素和非整合素受体的成纤维细胞迁移纤连蛋白。这种迁移的严格性很可能对正常间充质细胞在未受干扰的组织中的移动性施加了巨大的限制。这种限制的丧失对于癌细胞通过细胞外基质的迁移可能是至关重要的。
Mesenchymal cell movement is normally constrained; however, fibronectin can provide a pathway for stromal cell migration during embryogenesis, morphogenesis, and wound healing. Cells can adhere to fibronectin via integrin and nonintegrin receptors, which bind multiple unique peptide sequences. Synthetic peptides and recombinant proteins were used to delineate the functional domains needed for human fibroblast migration over fibronectin. The 9th and 10th fibronectin type III repeats, which contain RGD and PHSRN synergy cell attachment sequences, support almost maximal fibroblast attachment, but not migration of primary dermal fibroblasts. Specific sequences within the heparin domain and the IIICS region are also required for migration. These findings predict and additional data confirm the necessity for the cooperation of multiple integrin and nonintegrin receptors for fibroblast migration on fibronectin. Such stringency of migration most likely imposes an immense constraint on normal mesenchymal cell mobility in unperturbed tissue. Loss of such restraint may be critical for the migration cancer cells through the extracellular matrix.