Abstract
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 ovarian cancer. While their exact role in ovarian tumors is still being elucidated, these proteins are thought to be critical for ovarian cancer cell invasion/dissemination and resistance to chemotherapy. Claudin-3 and claudin-4 are the natural receptors for the Clostridium perfringens enterotoxin (CPE), a potent cytolytic toxin. These surface proteins may therefore represent attractive targets for the detection and treatment of chemotherapy-resistant ovarian cancer and other aggressive solid tumors overexpressing claudin-3 and -4 using CPE-based theranostic agents.
Highlights
Claudins are a family of tight junctional proteins which are highly expressed in both benign and malignant ovarian tumors [1]
The results showed that the serum and ascites of preoperative ovarian cancer patients had increased levels of vascular endothelial growth factor (VEGF) and that there was a VEGF-dependent decrease of claudin-5 in endothelial cells co-cultured with ovarian cancer cells
The results suggest that one mechanism by which VEGF may induce ascites formation in ovarian cancer patients is by increasing peritoneal permeability secondary to the downregulation of the tight junctions (TJs) protein claudin-5 in the peritoneal endothelium [119]
Summary
Claudins are a family of tight junctional proteins which are highly expressed in both benign and malignant ovarian tumors [1]. TJs are comprised of multiple membrane proteins such as occludin and claudin family proteins and several other associated peripheral proteins such as zonula occludens 1-3 (ZO-1, -2 and -3) [3,4]. These proteins are seen at the cell membrane interface where they contribute to the formation of the TJ and interact to form the diffusion barrier. The delocalization of claudin proteins from cell membranes is common among transformed cells and in ovarian cancer this is associated with tumor cell migration and invasion [10,13]. Some claudins have been shown to have a prognostic role in particular tumor types, for example, claudin-3/-4 has a prognostic role in ovarian cancer, claudin-1 in colon cancer, claudin-10 in hepatocellular carcinoma and claudin-18 in gastric cancer [28,29,30,31]
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