Binding of ovarian cancer antigen CA125/MUC16 to mesothelin mediates cell adhesion
Binding of ovarian cancer antigen CA125/MUC16 to mesothelin mediates cell adhesion
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DOI：
10.1074/jbc.m312372200
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发表时间：
2004-03-05
影响因子：
4.8
通讯作者：
Miyajima, A
中科院分区：
文献类型：
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作者：
Rump, A;Morikawa, Y;Miyajima, A
间硫蛋白是一种糖基磷脂酰肌醇连接的细胞表面分子，表达于体腔的间皮衬里和许多肿瘤细胞中。基于一种可溶性间硫蛋白与卵巢癌细胞株OVCAR-3特异结合的发现，我们通过表达克隆的方法分离了编码间硫蛋白结合蛋白的cDNAs。这两个克隆的cDNA片段编码的多肽与卵巢癌抗原CA125的一部分匹配，CA125是一种存在于肿瘤细胞表面的巨型粘蛋白样糖蛋白。通过流式细胞仪分析和免疫沉淀，我们证明了CA125以一种特定的方式与间硫蛋白结合。当抗间硫蛋白抗体阻断表达CA125的OVCAR-3细胞与表达间硫蛋白的内皮样细胞系的结合时，CA125与膜结合间皮蛋白的结合介导了异型细胞黏附。最后，我们发现CA125和间充质蛋白在晚期卵巢腺癌中共同表达。综上所述，我们的研究结果表明，间皮蛋白是一种新的CA125结合蛋白，CA125可能通过与间皮蛋白结合而启动细胞与间皮细胞的附着，从而促进卵巢癌向腹膜的转移。
Mesothelin is a glycosylphosphatidylinositol-linked cell surface molecule expressed in the mesothelial lining of the body cavities and in many tumor cells. Based on the finding that a soluble form of mesothelin specifically binds to ovarian carcinoma cell line OVCAR-3, we isolated cDNAs encoding a mesothelin-binding protein by expression cloning. The polypeptides encoded by the two cloned cDNA fragments matched to portions of CA125, an ovarian cancer antigen and a giant mucin-like glycoprotein present at the surface of tumor cells. By flow cytometric analysis and immunoprecipitation, we demonstrate that CA125 binds to mesothelin in a specific manner. Binding of CA125 to membrane-bound mesothelin mediates heterotypic cell adhesion as anti-mesothelin antibody blocks binding of OVCAR-3 cells expressing CA125 to an endothelial-like cell line expressing mesothelin. Finally, we show that CA125 and mesothelin are co-expressed in advanced grade ovarian adenocarcinoma. Taken together, our data indicate that mesothelin is a novel CA125-binding protein and that CA125 might contribute to the metastasis of ovarian cancer to the peritoneum by initiating cell attachment to the mesothelial epithelium via binding to mesothelin.