Patel Ila S, Madan Pavneesh, Getsios Spiro, Bertrand Monique A, MacCalman Colin D
Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, British Columbia, Canada.
Int J Cancer. 2003 Aug 20;106(2):172-7. doi: 10.1002/ijc.11086.
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.
当恶性细胞已在腹腔内播散，钙黏蛋白在卵巢癌进展至疾病晚期阶段所起的作用仍知之甚少。鉴于这些观察结果，我们采用简并克隆策略，针对这一家族细胞黏附分子中高度保守的序列，对正常卵巢表面上皮、腹膜以及诊断为Ⅰ期或Ⅱ期原发性卵巢癌的女性患者的肿瘤及腹腔积液中存在的钙黏蛋白亚型进行了全面调查。根据所得PCR产物的核苷酸序列，发现多种钙黏蛋白亚型（E-、N-、P-钙黏蛋白以及钙黏蛋白-4、-6和-11）存在于这些正常和恶性组织及细胞中。已确定P-钙黏蛋白是正常腹膜、腹腔积液和Ⅱ期肿瘤块中的主要钙黏蛋白亚型。Northern印迹和Western印迹分析分别证实，随着疾病进展至晚期，卵巢肿瘤块中P-钙黏蛋白的mRNA和蛋白表达水平增加。此外，我们还确定，被称为β-连环蛋白的钙黏蛋白相关蛋白在正常腹膜、卵巢肿瘤以及从Ⅰ期或Ⅱ期癌症女性患者获得的恶性细胞积液中表达。免疫沉淀研究表明，在这些正常和恶性组织及细胞中，P-钙黏蛋白能够与β-连环蛋白相互作用。总体而言，这些发现表明，卵巢肿瘤细胞中P-钙黏蛋白/β-连环蛋白复合物的调控表达可能是疾病进展的关键步骤。
