Veatch A L, Carson L F, Ramakrishnan S
Department of Pharmacology, University of Minnesota, Minneapolis 55455.
Int J Cancer. 1994 Aug 1;58(3):393-9. doi: 10.1002/ijc.2910580315.
Advanced ovarian cancers contain 2 distinct phenotypic populations: (a) free-floating tumor cells in the ascitic fluid and (b) solid tumors. Ascites cells are derived from the solid tumors and spread throughout the peritoneum. Changes in cell-cell and cell-extracellular matrix interactions are thought to be responsible for the origin of ascites cells. Since E-cadherin molecules play a crucial role in the cell-cell interactions in epithelial cells, we investigated the expression of E-cadherin in these 2 phenotypic populations. Paired samples of ascites and solid tumors were obtained from patients. Both primary tumors and tumor cells isolated from an experimental model showed a marked decrease in E-cadherin expression in the ascites cells compared to the respective solid tumors. Semi-quantitative, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to determine the steady-state levels of E-cadherin-specific mRNA. Results indicate that the primary tumors had significantly lower levels of E-cadherin transcript in ascites cells when compared to their solid tumor counterparts. Changes in E-cadherin expression were also reflected in the invasion capacity of tumor cells in vitro. Ascites cells were 4-fold more invasive then solid tumor cells, suggesting that ascites cells are a highly malignant phenotype.
(a)腹水中的游离肿瘤细胞和(b)实体瘤。腹水细胞源自实体瘤并扩散至整个腹膜。细胞间以及细胞与细胞外基质相互作用的改变被认为是腹水细胞产生的原因。由于E-钙黏蛋白分子在上皮细胞的细胞间相互作用中起关键作用,我们研究了这两种表型群体中E-钙黏蛋白的表达情况。从患者身上获取了腹水和实体瘤的配对样本。与各自的实体瘤相比,从实验模型中分离出的原发性肿瘤和肿瘤细胞在腹水细胞中的E-钙黏蛋白表达均显著降低。采用半定量逆转录聚合酶链反应(RT-PCR)来测定E-钙黏蛋白特异性mRNA的稳态水平。结果表明,与实体瘤对应部分相比,原发性肿瘤在腹水细胞中的E-钙黏蛋白转录水平显著更低。E-钙黏蛋白表达的变化也反映在肿瘤细胞的体外侵袭能力上。腹水细胞的侵袭性比实体瘤细胞高4倍,这表明腹水细胞是一种高度恶性的表型。