Laminin isoforms and their integrin receptors in glioma cell migration and invasiveness:: Evidence for a role of α5-laminin(s) and α3β1 integrin
Laminin isoforms and their integrin receptors in glioma cell migration and invasiveness:: Evidence for a role of α5-laminin(s) and α3β1 integrin
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DOI：
10.1016/j.yexcr.2007.07.038
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发表时间：
2007-11-01
影响因子：
3.7
通讯作者：
Patarroyo, Manuel
中科院分区：
文献类型：
--
作者：
Kawataki, Tomoyuki;Yamane, Tetsu;Patarroyo, Manuel
脑组织的胶质瘤细胞浸润常发生于沿着血管基底膜（BM）。在本研究中，我们研究了层粘连蛋白的作用，层粘连蛋白是BM的主要结构成分，也是细胞迁移的强促进剂。神经胶质瘤肿瘤组织的免疫组织化学研究表明肿瘤血管系统表达α 2-、α 3-、α 4-和α 5-层粘连蛋白，但不表达α 1-层粘连蛋白。在功能测定中，α 3（Lm-332/层粘连蛋白-5）-和α 5（Lm-511/层粘连蛋白-10）-层粘连蛋白强烈促进所有测试的胶质瘤细胞系的迁移。α 1-层粘连蛋白（Lm-111/层粘连蛋白-1）显示出较低的活性，而α 2（Lm-211/层粘连蛋白-2）-和α 4（Lm-411/层粘连蛋白-8）-层粘连蛋白实际上无活性。整体整合素表型鉴定α 3 β 1为所有胶质瘤细胞系中最丰富的整合素，并且这种层粘连蛋白结合整合素专门或主要介导细胞迁移。此外，用α 3 β 1整合素的阻断抗体预处理U251胶质瘤细胞，然后脑内注射到裸鼠中，抑制了肿瘤细胞向脑组织的侵袭。细胞系以不同的比例分泌Lm-211、Lm-411和Lm-511。结果表明神经胶质瘤细胞分泌α 2-、α 4-和α 5-层粘连蛋白，并且在脑血管系统中发现的α 3-和α 5-层粘连蛋白选择性地促进神经胶质瘤细胞迁移。他们确定α 3 β 1是胶质瘤细胞中主要的整合素和层粘连蛋白受体，也是介导脑侵袭的整合素。(C)2007年爱思唯尔公司All rights reserved.
Glioma cell infiltration of brain tissue often occurs along the basement membrane (BM) of blood vessels. in the present study we have investigated the role of laminins, major structural components of BMs and strong promoters of cell migration. Immunohistochemical studies of glioma tumor tissue demonstrated expression of alpha 2-, alpha 3-, alpha 4- and alpha 5-, but not alpha 1-, laminins by the tumor vasculature. In functional assays, alpha 3 (Lm-332/laminin-5)- and alpha 5 (Lm-511/laminin-10)-laminins strongly promoted migration of all glioma cell lines tested. alpha 1-Laminin (Lm-111/laminin-1) displayed lower activity, whereas alpha 2 (Lm-211/laminin-2)- and alpha 4 (Lm-411/laminin-8)-laminins were practically inactive. Global integrin phenotyping identified alpha 3 beta 1 as the most abundant integrin in all the glioma cell lines, and this laminin-binding integrin exclusively or largely mediate the cell migration. Moreover, pretreatment of U251 glioma cells with blocking antibodies to alpha 3 beta 1 integrin followed by intracerebral injection into nude mice inhibited invasion of the tumor cells into the brain tissue. The cell lines secreted Lm-211, Lm-411 and Lm-511, at different ratios. The results indicate that glioma cells secrete alpha 2-, alpha 4- and alpha 5-laminins and that alpha 3- and alpha 5-laminins, found in brain vasculature, selectively promote glioma cell migration. They identify alpha 3 beta 1 as the predominant integrin and laminin receptor in glioma cells, and as a brain invasion-mediating integrin. (C) 2007 Elsevier Inc. All rights reserved.