Cadherin switching in ovarian cancer progression
Cadherin switching in ovarian cancer progression
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DOI：
10.1002/ijc.11086
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发表时间：
2003-08-20
影响因子：
6.4
通讯作者：
MacCalman, CD
中科院分区：
文献类型：
--
作者：
Patel, IS;Madan, P;MacCalman, CD
钙粘蛋白在卵巢癌进展到晚期的疾病状态时，恶性细胞已在腹膜腔内扩散的作用仍然知之甚少。鉴于这些观察结果，我们已经进行了一项全面的调查，目前在正常卵巢表面上皮和腹膜，并在肿瘤和腹膜渗出液的妇女诊断为第一阶段或第二阶段的原发性卵巢癌，使用简并克隆策略的序列高度保守的细胞粘附分子家族。基于所得PCR产物的核苷酸序列，发现在这些正常和恶性组织和细胞中存在多种钙粘蛋白亚型（E-、N-、P-钙粘蛋白和钙粘蛋白-4、-6和-11）。P-钙粘蛋白被确定为在正常腹膜、腹膜积液和II期肿瘤肿块中的主要钙粘蛋白亚型。北方和Western印迹分析分别证实了随着疾病进展，卵巢肿瘤肿块中P-钙粘蛋白mRNA和蛋白表达水平的增加。此外，我们已经确定，钙粘蛋白相关蛋白，称为β-连环蛋白，表达在正常腹膜，卵巢肿瘤和恶性细胞渗出液获得的妇女与第一阶段或第二阶段癌症。免疫沉淀研究表明，P-钙粘蛋白能够与β-连环蛋白在这些正常和恶性组织和细胞相互作用。总的来说，这些发现表明卵巢肿瘤细胞中P-钙粘蛋白/β-连环蛋白复合物的调节表达可能是疾病进展的关键一步。(C)2003 Wiley-Liss，Inc.
The roles of the cadherins in the progression of ovarian cancer to the late stages of the disease state when malignant cells have disseminated within the peritoneal cavity remain poorly understood. In view of these observations, we have undertaken a comprehensive survey of the cadherin subtypes present in normal ovarian surface epithelium and peritoneum and in the tumors and peritoneal effusions of women diagnosed with Stage I or Stage II primary ovarian cancer using a degenerate cloning strategy for sequences highly conserved among this family of cell adhesion molecules. On the basis of the nucleotide sequences of the resultant PCR products, multiple cadherin subtypes (E-, N-, P-cadherin, and cadherin-4, -6, and -11) were found to be present in these normal and malignant tissues and cells. P-cadherin was determined to be the predominant cadherin subtype in normal peritoneum, peritoneal effusions and Stage II tumor masses. An increase in P-cadherin mRNA and protein expression levels in ovarian tumor masses with progression to later stages of the disease state was confirmed by Northern and Western blot analysis, respectively. In addition, we have determined that the cadherin-associated protein, known as beta-catenin, is expressed in normal peritoneum, ovarian tumors and malignant cell effusions obtained from women with Stage I or Stage II cancer. Immunoprecipitation studies demonstrated that P-cadherin was capable of interacting with beta-catenin in these normal and malignant tissues and cells. Collectively, these findings suggest that the regulated expression of P-cadherin/beta-catenin complexes in ovarian tumor cells may represent a key step in disease progression. (C) 2003 Wiley-Liss, Inc.