Cancer Therapy: Preclinical C Terminus of Clostridium perfringens Enterotoxin Downregulates CLDN4 and Sensitizes Ovarian Cancer Cells to Taxol and Carboplatin
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چکیده
Purpose: We have previously shown that CLDN4 (encoding claudin-4), a cell tight junction (TJ) protein, is highly expressed in human epithelial ovarian carcinomas (EOC) but undetectable in normal ovaries. CLDN4 has been identified as a specific receptor for C terminus of Clostridium perfringens enterotoxin (C-CPE), a nontoxic molecule that may disrupt TJ barrier function and enhance cellular absorption. The purpose of this study was to determine the potential clinical applications of C-CPE and its effects on CLDN4 expression in EOC. Experimental Design: Using a 3-dimensional culture model and monolayer culture of EOC cells, we examined the effects of C-CPE on CLDN4 expression by quantitative real-time PCR, immunofluorescence, and Western blot. The synergistic effect of C-CPE to clinically relevant chemotherapies (Taxol and Carboplatin) was observed in EOC culture and xenograft mice. Furthermore, we determined through oligonucleotide microarray analysis that the transcript profile alterations dysregulated as a consequence of
منابع مشابه
C terminus of Clostridium perfringens enterotoxin downregulates CLDN4 and sensitizes ovarian cancer cells to Taxol and Carboplatin.
PURPOSE We have previously shown that CLDN4 (encoding claudin-4), a cell tight junction (TJ) protein, is highly expressed in human epithelial ovarian carcinomas (EOC) but undetectable in normal ovaries. CLDN4 has been identified as a specific receptor for C terminus of Clostridium perfringens enterotoxin (C-CPE), a nontoxic molecule that may disrupt TJ barrier function and enhance cellular abso...
متن کاملRecombinant CPE fused to tumor necrosis factor targets human ovarian cancer cells expressing the claudin-3 and claudin-4 receptors.
Using gene expression profiling, others and we have recently found that claudin-3 (CLDN3) and claudin-4 (CLDN4) are two of the most highly and consistently up-regulated genes in ovarian carcinomas. Because these tight junction proteins are the naturally occurring receptors for Clostridium perfringens enterotoxin (CPE), in this study, we used the COOH-terminal 30 amino acids of the CPE (CPE(290-...
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Claudins are a family of tight junction proteins regulating paracellular permeability and cell polarity with different patterns of expression in benign and malignant human tissues. There are approximately 27 members of the claudin family identified to date with varying cell and tissue-specific expression. Claudins-3, -4 and -7 represent the most highly differentially expressed claudins in ovari...
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Background: Clostridium perfringens is known as the most widely distributed pathogenic microorganism in nature. It is an extremely important pathogen of human and domestic animals. In a commonly used classification scheme, C. perfringens is divided into five toxinotypes (A to E) based on the production of four major toxins (alpha, beta, epsilon, and iota). Enterotoxin is not usually used for C....
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تاریخ انتشار 2011