Functional differences between integrin alpha4 and integrins alpha5/alphav in modulating the motility of human oral squamous carcinoma cells in response to the V region and heparin-binding domain of fibronectin.
Functional differences between integrin alpha4 and integrins alpha5/alphav in modulating the motility of human oral squamous carcinoma cells in response to the V region and heparin-binding domain of fibronectin.
复制标题
整合素α4和整合素α5/αv在调节人口腔鳞状癌细胞响应纤连蛋白V区和肝素结合域的运动方面的功能差异。
DOI：
10.1016/j.yexcr.2003.12.011
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Kapila,Yvonne
中科院分区：
文献类型：
--
作者：
Zhang,Yan;Lu,Hai;Dazin,Paul;Kapila,Yvonne
The high-affinity heparin-binding domain and the V region of fibronectin (FN) mediate invasion and migration of human oral squamous cell carcinoma (SCC) cells. We investigated the role of the α4, α5, and αv integrin receptors—which are central to mediating interactions with these domains of FN—in regulating SCC cell migration. SCC cells expressed the α4, α5, and αv integrin subunits on their surface, although α4 expression was low. Treatment with recombinant FN proteins containing an alternatively spliced V region (V+) and either an unmutated (H+) or a mutated, nonfunctional high-affinity heparin-binding domain (H−) increased expression of α5 and αv and cell motility. Antisense α5 or αv oligonucleotides inhibited cell motility stimulated by FN proteins, as did blocking antibodies to α5 or αv. Blocking antibodies to α5 increased αv and α4 levels, and blocking antibodies to αv increased the levels of α5 and α4, without increasing cell motility. In contrast, an antisense α4 oligonucleotide and α4-blocking antibodies increased cell motility, especially migration stimulated by V+H+ and V+H− FN proteins. α4-Blocking antibodies alone increased motility, probably by inducing α5 and αv expression. Transfection with α4 cDNA decreased cell motility and α5 and αv expression. Thus, the increased motility induced by the FN protein is probably mediated by αv and α5, whereas α4 downregulates this process in a transdominant fashion.
