LAMININ RECEPTOR ON HUMAN-BREAST CARCINOMA-CELLS
LAMININ RECEPTOR ON HUMAN-BREAST CARCINOMA-CELLS
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DOI：
10.1073/pnas.80.2.444
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发表时间：
1983-01-01
期刊：
影响因子：
--
通讯作者：
LIOTTA, LA
中科院分区：
文献类型：
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作者：
TERRANOVA, VP;RAO, CN;LIOTTA, LA
人MCF-7乳腺癌细胞在其表面上具有受体样部分，其对层粘连蛋白（一种位于基底膜中的糖蛋白）具有高结合亲和力（Kd = 2 nM）。层粘连蛋白优先刺激（8倍）MCF-7细胞附着于IV型（基底膜）胶原，而纤连蛋白仅刺激这些细胞在I型胶原上的附着2倍。另外两个人乳腺癌细胞系IV型胶原的附着特性进行了研究。ZR-75 - 1细胞的粘附被层粘连蛋白刺激4倍，被纤连蛋白刺激5倍，而T47-D细胞的粘附被层粘连蛋白刺激2倍，被纤连蛋白刺激7倍。通过使用层粘连蛋白的蛋白酶衍生片段，鉴定了参与MCF-7细胞附着至IV型胶原的层粘连蛋白分子的主要结构域。整个层粘连蛋白分子具有四臂交叉的构型，具有三个短臂和一个长臂。发现一个主要的细胞结合结构域位于短臂的交叉点附近，IV型胶原结合结构域与短臂的球形末端区域相关。这些肿瘤细胞表面的层粘连蛋白受体可能参与肿瘤细胞通过层粘连蛋白与血管基底膜的初始相互作用，以促进侵袭和随后的转移促进。
Human MCF-7 breast carcinoma cells possess a receptor-like moiety on their surface that has a high binding affinity (Kd = 2 nM) for laminin, a glycoprotein localized in basement membranes. Laminin preferentially stimulates (8-fold) MCF-7 cells to attach to type IV (basement membrane) collagen, whereas fibronectin stimulates attachment only 2-fold for these cells on type I collagen. The attachment properties of two other human breast carcinoma cell lines to type IV collagen were also studied. The attachment of ZR-75-1 cells was stimulated 4-fold by laminin and 5-fold by fibronectin, whereas T47-D cell attachment was stimulated 2-fold by laminin and 7-fold by fibronectin. By employing protease-derived fragments of laminin, the major domains of the laminin molecule that participate in MCF-7 cell attachment to type IV collagen were identified. The whole laminin molecule has the configuration of a four-armed cross with three short arms and one long arm. A major cell-binding domain was found to reside near the intersection point of the short arms, and the type IV collagen-binding domain was associated with the globular end regions of the short arms. The receptor for laminin on the surface of these tumor cells may be involved in the initial interaction of tumor cells via laminin with the vascular basement membrane to facilitate invasion and subsequent promotion of metastasis.