Lotz M M, Korzelius C A, Mercurio A M
Laboratory of Cancer Biology, New England Deaconess Hospital, Harvard Medical School, Boston, MA 02115.
Cell Regul. 1990 Feb;1(3):249-57. doi: 10.1091/mbc.1.3.249.
In this study, we used clone A, a human colon carcinoma cell line, to characterize those integrins that mediate colon carcinoma adhesion to laminin. Monoclonal antibodies specific for the human beta 1 subunit inhibited clone A adhesion to laminin. They also precipitated a complex of surface proteins that exhibited an electrophoretic behavior characteristic of alpha 2 beta 1 and alpha 3 beta 1. A monoclonal antibody specific for alpha 2 (PIH5) blocked clone A adhesion to laminin, as well as to collagen I. An alpha 3-specific antibody (P1B5) had no effect on clone A adhesion to laminin, even though it can block the adhesion of other cell types to laminin. Thus, the alpha 2 beta 1 integrin can function as both a laminin and collagen I receptor on clone A cells. Although these cells express alpha 3 beta 1, an established laminin receptor, they do not appear to use it to mediate laminin adhesion. In addition, the monoclonal antibody GoH3, which recognizes the alpha 6 integrin subunit, also inhibited carcinoma adhesion to laminin but not to fibronectin or collagen I. This antibody precipitated the alpha 6 subunit in association with the beta 4 subunit. There was no evidence of alpha 6 beta 1 association on these cells. In summary, the results obtained in this study indicate that multiple integrin alpha subunits, in association with two distinct beta subunits, are involved in colon carcinoma adhesion to laminin. Based on the behavior of alpha 3 beta 1 and alpha 2 beta 1, the results also suggest that cells can regulate the ability of a specific integrin to mediate adhesion.
在本研究中，我们使用克隆A（一种人结肠癌细胞系）来鉴定介导结肠癌细胞与层粘连蛋白黏附的整合素。针对人β1亚基的单克隆抗体抑制了克隆A与层粘连蛋白的黏附。它们还沉淀出一种表面蛋白复合物，该复合物表现出α2β1和α3β1的电泳行为特征。针对α2的单克隆抗体（PIH5）阻断了克隆A与层粘连蛋白以及与I型胶原的黏附。一种α3特异性抗体（P1B5）对克隆A与层粘连蛋白的黏附没有影响，尽管它可以阻断其他细胞类型与层粘连蛋白的黏附。因此，α2β1整合素在克隆A细胞上既可以作为层粘连蛋白受体，也可以作为I型胶原受体发挥作用。尽管这些细胞表达α3β1（一种已确定的层粘连蛋白受体），但它们似乎并未利用它来介导与层粘连蛋白的黏附。此外，识别α6整合素亚基的单克隆抗体GoH3也抑制了癌细胞与层粘连蛋白的黏附，但不影响与纤连蛋白或I型胶原的黏附。该抗体沉淀出与β4亚基相关的α6亚基。在这些细胞上没有α6β1缔合的证据。总之，本研究获得的结果表明，多个整合素α亚基与两个不同的β亚基缔合，参与了结肠癌细胞与层粘连蛋白的黏附。基于α3β1和α2β1的行为，结果还表明细胞可以调节特定整合素介导黏附的能力。
