Episialin (MUC1) overexpression inhibits integrin-mediated cell adhesion to extracellular matrix components.
Episialin (MUC1) overexpression inhibits integrin-mediated cell adhesion to extracellular matrix components.
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DOI：
10.1083/jcb.129.1.255
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发表时间：
1995-04
期刊：
影响因子：
--
通讯作者：
Hilkens J
中科院分区：
文献类型：
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作者：
Wesseling J;van der Valk SW;Vos HL;Sonnenberg A;Hilkens J
上皮唾液酸蛋白（MUC 1）是一种跨膜分子，具有一个大的粘蛋白样细胞外结构域，突出于细胞表面上方。该分子位于大多数腺上皮细胞的顶侧，而在癌细胞中，它通常存在于整个表面，并且经常以异常大量表达。我们先前已经表明，episialin的过度表达减少细胞间的相互作用。在这里，我们表明，整合素介导的粘附细胞外基质的转染的黑色素瘤细胞系（A375），转化的上皮细胞系（MDCK-ras-e）和人乳腺上皮细胞系（HBL-100）是减少高水平的episialin。这种减少可以通过mAb TS 2/16诱导β 1整联蛋白的高亲合力来逆转（至少对于β 1介导的粘附）。粘附也可以通过单克隆抗体将细胞表面上的episialin重新分布成贴片或帽来恢复。类似地，在悬浮液中生长的ZR-75-1乳腺癌细胞上的episialin的加帽引起这些细胞的粘附和扩散。我们提出，在表达episialin的细胞中，粘附力和抗粘附力之间存在微妙的平衡，这可以通过加强整合素介导的粘附而转向粘附，或者通过增加episialin的表达水平而转向抗粘附。
Episialin (MUC1) is a transmembrane molecule with a large mucin-like extracellular domain protruding high above the cell surface. The molecule is located at the apical side of most glandular epithelial cells, whereas in carcinoma cells it is often present at the entire surface and it is frequently expressed in abnormally large quantities. We have previously shown that overexpression of episialin reduces cell- cell interactions. Here we show that the integrin-mediated adhesion to extracellular matrix of transfectants of a melanoma cell line (A375), a transformed epithelial cell line (MDCK-ras-e) and a human breast epithelial cell line (HBL-100) is reduced by high levels of episialin. This reduction can be reversed by inducing high avidity of the beta 1 integrins by mAb TS2/16 (at least for beta 1-mediated adhesion). The adhesion can also be restored by redistribution of episialin on the cell surface by monoclonal antibodies into patches or caps. Similarly, capping of episialin on ZR-75-1 breast carcinoma cells, growing in suspension, caused adherence and spreading of these cells. We propose that there is a delicate balance between adhesion and anti-adhesion forces in episialin expressing cells, which can be shifted towards adhesion by strengthening the integrin-mediated adhesion, or towards anti-adhesion by increasing the level of expression of episialin.