Wesseling J, van der Valk S W, Vos H L, Sonnenberg A, Hilkens J
Division of Tumor Biology, The Netherlands Cancer Institute (Antoni van Leeuwenhoekhuis), Amsterdam.
J Cell Biol. 1995 Apr;129(1):255-65. doi: 10.1083/jcb.129.1.255.
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.
唾液酸糖蛋白（MUC1）是一种跨膜分子，其具有一个大的黏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端，而在癌细胞中，它通常存在于整个细胞表面，并且经常大量异常表达。我们之前已经表明，唾液酸糖蛋白的过表达会减少细胞间相互作用。在此我们表明，高水平的唾液酸糖蛋白会降低黑色素瘤细胞系（A375）、转化上皮细胞系（MDCK-ras-e）和人乳腺上皮细胞系（HBL-100）转染子对细胞外基质的整合素介导的黏附。通过单克隆抗体TS2/16诱导β1整合素的高亲和力（至少对于β1介导的黏附），这种降低可以被逆转。通过单克隆抗体将唾液酸糖蛋白在细胞表面重新分布成斑块或帽状，黏附也可以恢复。同样，在悬浮培养的ZR-75-1乳腺癌细胞上唾液酸糖蛋白的帽化导致这些细胞的黏附和铺展。我们提出，在表达唾液酸糖蛋白的细胞中，黏附力和抗黏附力之间存在微妙的平衡，通过加强整合素介导的黏附可以使其向黏附方向转变，或者通过增加唾液酸糖蛋白的表达水平使其向抗黏附方向转变。
