From the Laboratory of Clinical Biochemistry, Tokyo University of Pharmacy and Life Sciences, Hachioji, 192-0392, Japan.
J Biol Chem. 2013 Oct 25;288(43):30990-1001. doi: 10.1074/jbc.M113.486456. Epub 2013 Sep 13.
Cell-matrix interactions are critical for tumor cell migration. Lutheran (Lu), also known as basal cell adhesion molecule (B-CAM), competes with integrins for binding to laminin α5, a subunit of LM-511, a major component of basement membranes. Here we show that the preferential binding of Lu/B-CAM to laminin α5 promotes tumor cell migration. The attachment of Lu/B-CAM transfectants to LM-511 was slightly weaker than that of control cells, and this was because Lu/B-CAM disturbed integrin binding to laminin α5. Lu/B-CAM induced a spindle cell shape with pseudopods and promoted cell migration on LM-511. In addition, blocking with an anti-Lu/B-CAM antibody led to a flat cell shape and inhibited migration on LM-511, similar to the effects of an activating integrin β1 antibody. We conclude that tumor cell migration on LM-511 requires that Lu/B-CAM competitively modulates cell attachment through integrins. We suggest that this competitive interaction is involved in a balance between static and migratory cell behaviors.
细胞-基质相互作用对于肿瘤细胞迁移至关重要。Lutheran（Lu），也称为基底细胞黏附分子（B-CAM），与整合素竞争与层粘连蛋白 α5 结合，层粘连蛋白 α5 是基底膜的主要成分 LM-511 的亚基。在这里，我们表明 Lu/B-CAM 与层粘连蛋白 α5 的优先结合促进了肿瘤细胞迁移。Lu/B-CAM 转染细胞与 LM-511 的附着比对照细胞略弱，这是因为 Lu/B-CAM 干扰了整合素与层粘连蛋白 α5 的结合。Lu/B-CAM 诱导具有伪足的纺锤形细胞形状，并促进细胞在 LM-511 上迁移。此外，用抗 Lu/B-CAM 抗体阻断导致细胞在 LM-511 上呈扁平形状并抑制迁移，类似于激活整合素 β1 抗体的作用。我们得出结论，肿瘤细胞在 LM-511 上的迁移需要 Lu/B-CAM 通过整合素竞争调节细胞附着。我们认为这种竞争相互作用涉及静态和迁移细胞行为之间的平衡。
