Qian Feng, Zhang Zi-Chao, Wu Xue-Feng, Li Yu-Pei, Xu Qiang
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Han Kou Road, Nanjing 210093, China.
Biochem Biophys Res Commun. 2005 Aug 12;333(4):1269-75. doi: 10.1016/j.bbrc.2005.06.039.
In this study, we report the role of integrin alpha(5) in promoting melanoma metastasis. The alpha(5) expression was remarkably elevated in highly metastatic B16F10 melanoma cells compared to lowly metastatic B16F1 cells, whereas no significant changes were detected in those of integrin alpha(4), alpha(v), and beta(1) subunits. Neutralization of alpha(5) with anti-alpha(5) antibody significantly suppressed the potential of B16F10 cells for pulmonary metastasis in mice and inhibited cell adhesion or spreading to fibronectin in vitro. Furthermore, loss of the interaction between alpha(5) and fibronectin diminished cell survival and induced apoptosis in B16F10 cells. Above results provide clear evidence that integrin alpha(5) is positively correlated with melanoma metastasis and might be an anti-melanoma target.
在本研究中,我们报告了整合素α(5)在促进黑色素瘤转移中的作用。与低转移的B16F1细胞相比,高转移的B16F10黑色素瘤细胞中α(5)的表达显著升高,而整合素α(4)、α(v)和β(1)亚基的表达未检测到明显变化。用抗α(5)抗体中和α(5)可显著抑制B16F10细胞在小鼠体内的肺转移潜能,并在体外抑制细胞对纤连蛋白的黏附或铺展。此外,α(5)与纤连蛋白之间相互作用的丧失降低了B16F10细胞的存活率并诱导其凋亡。上述结果提供了明确的证据,表明整合素α(5)与黑色素瘤转移呈正相关,可能是一个抗黑色素瘤靶点。