EVIDENCE FOR A ROLE OF THE EPITHELIAL GLYCOPROTEIN-40 (EP-CAM) IN EPITHELIAL CELL-CELL ADHESION
EVIDENCE FOR A ROLE OF THE EPITHELIAL GLYCOPROTEIN-40 (EP-CAM) IN EPITHELIAL CELL-CELL ADHESION
复制标题
DOI：
10.3109/15419069409004452
复制
发表时间：
1994-01-01
期刊：
影响因子：
--
通讯作者：
WARNAAR, SO
中科院分区：
文献类型：
--
作者：
LITVINOV, SV;BAKKER, HAM;WARNAAR, SO
最近，我们已经证明了40kD的人上皮特异性糖蛋白在转基因小鼠细胞中表达时，表现出血友病细胞-细胞黏附分子的特征。我们建议将该分子命名为EP-CAM(Litvinov等人，J.Cell Biol.，125：437-446)。在这里，我们研究了EP-CAM在其自然环境--上皮源性细胞--中可能的生物学功能。EP-CAM在组织和上皮/癌细胞培养中的免疫定位表明，大多数EP-CAM分子定位于细胞-细胞边界，主要分布在极化细胞的整个侧域。在体外，在悬浮的单个细胞上，EP-CAM分子存在于整个细胞表面，当单个细胞附着生长时，EP-CAM存在于它们的伪尖端域。在这种单个细胞形成细胞间接触的过程中，大多数EP-CAM分子从细胞膜的假尖区域重新分布到细胞膜的侧域。细胞与底物的附着不会导致分子重新分布到底物附着的位置，而与粘连底物无关(测试了纤维连接蛋白、胶原蛋白、层粘连蛋白、EHS-Matrigel)。与EP-CAM分子胞外区结合的单抗323/A3对COV362卵巢癌细胞和RC-6永生化乳腺上皮细胞的聚集行为有强烈的负面影响。在钙离子存在的情况下，单抗对两种细胞系的细胞聚集均有影响，但对RC-6细胞的影响在低钙条件下更为明显。323/A3单抗对已建立的细胞间接触的影响不显著。这些数据表明，EP-CAM分子在被测试的上皮细胞和癌细胞中具有功能活性，能够介导钙离子非依赖性的细胞间黏附，而不太可能参与细胞与基质的黏附。
Recently we have demonstrated that a 40kD human epithelium-specific glycoprotein exhibits the features of a hemophilic cell-cell adhesion molecule, when expressed in transfected murine cells. We suggested the name Ep-CAM for this molecule (Litvinov et al., J. Cell Biol., 125: 437-446). Here we investigate the possible biological function of Ep-CAM in its natural environment-cells of epithelial origin. Immunolocalization of Ep-CAM in tissues and in cultures of epithelial/carcinoma cells showed that the majority of the Ep-CAM molecules are localized at cell-cell boundaries, predominantly along the whole lateral domain of polarized cells. In vitro, on single cells in suspension, the Ep-CAM molecules are present on the entire cell surface, and when the single cells grow attached, Ep-CAM is present at their pseudo-apical domain. During formation of intercellular contacts by such single cells, the majority of the Ep-CAM molecules are redistributed from the pseudoapical to the lateral domain of the cell membrane. Attachment of cells to the substrate does not cause redistribution of the molecules to the site of substrate attachment irrespective of the adhesive substrate (fibronectin, collagens, laminin, EHS-matrigel were tested). The monoclonal antibody 323/A3, reactive with the extracellular domain of the Ep-CAM molecule, has a strong negative effect on the aggregating behaviour of COV362 ovarian carcinoma cells and RC-6 immortalized mammary epithelial cells. The mAb affected cell aggregation in both cell lines in the presence of Ca++, but with RC-6 cells the effect was more pronounced in low-calcium medium. The effects of the 323/A3 mAb on the already established intercellular contacts was not significant. The data presented demonstrate that the Ep-CAM molecules are functionally active in the epithelial and carcinoma cells tested, are capable of mediating Ca++-independent intercellular adhesions, and are not likely to be involved in cell-substrate adhesion.