Claudin-7 Is Frequently Overexpressed in Ovarian Cancer and Promotes Invasion

Background: Claudins are tight junction proteins that are involved in tight junction formation and function. Previous studies have shown that claudin-7 is frequently upregulated in epithelial ovarian cancer (EOC) along with claudin-3 and claudin-4. Here, we investigate in detail the expression patterns of claudin-7, as well as its possible functions in EOC. Methodology/Principal Findings: A total of 95 ovarian tissue samples (7 normal ovarian tissues, 65 serous carcinomas, 11 clear cell carcinomas, 8 endometrioid carcinomas and 4 mucinous carcinomas) were studied for claudin-7 expression. In real-time RT-PCR analysis, the gene for claudin-7, CLDN7, was found to be upregulated in all the tumor tissue samples studied. Similarly, immunohistochemical analysis and western blotting showed that claudin-7 protein was significantly overexpressed in the vast majority of EOCs. Small interfering RNA-mediated knockdown of claudin-7 in ovarian cancer cells led to significant changes in gene expression as measured by microarrays and validated by RT-PCR and immunoblotting. Analyses of the genes differentially expressed revealed that the genes altered in response to claudin-7 knockdown were associated with pathways implicated in various molecular and cellular functions such as cell cycle, cellular growth and proliferation, cell death, development, and cell movement. Through functional experiments in vitro, we found that both migration and invasion were altered in cells where CLDN7 had been knocked down or overexpressed. Interestingly, claudin-7 expression was associated with a net increase in invasion, but also with a decrease in migration

Tight junctions and the modulation of barrier function in disease

Tight junctions create a paracellular barrier in epithelial and endothelial cells protecting them from the external environment. Two different classes of integral membrane proteins constitute the tight junction strands in epithelial cells and endothelial cells, occludin and members of the claudin protein family. In addition, cytoplasmic scaffolding molecules associated with these junctions regulate diverse physiological processes like proliferation, cell polarity and regulated diffusion. In many diseases, disruption of this regulated barrier occurs. This review will briefly describe the molecular composition of the tight junctions and then present evidence of the link between tight junction dysfunction and disease

The Role of Adhesion Molecules as Biomarkers for the Aggressive Prostate Cancer Phenotype

BACKGROUND: Currently available methods for diagnosis and staging of prostate cancer lack the sensitivity to distinguish between patients with indolent prostate cancer and those requiring radical treatment. Alterations in key adherens (AJ) and tight junction (TJ) components have been hailed as potential biomarkers for prostate cancer progression but the majority of research has been carried out on individual molecules. OBJECTIVE: To elucidate a panel of biomarkers that may help distinguish dormant prostate cancer from aggressive metastatic disease. METHODS: We analysed the expression of 7 well known AJ and TJ components in cell lines derived from normal prostate epithelial tissue (PNT2), non-invasive (CAHPV-10) and invasive prostate cancer (LNCaP, DU145, PC-3) using gene expression, western blotting and immunofluorescence techniques. RESULTS: Claudin 7, α -catenin and β-catenin protein expression were not significantly different between CAHPV-10 cells and PNT2 cells. However, in PC-3 cells, protein levels for claudin 7, α -catenin were significantly down regulated (-1.5 fold, p = <.001) or undetectable respectively. Immunofluoresence showed β-catenin localisation in PC-3 cells to be cytoplasmic as opposed to membraneous. CONCLUSION: These results suggest aberrant Claudin 7, α - and β-catenin expression and/or localisation patterns may be putative markers for distinguishing localised prostate cancer from aggressive metastatic disease when used collectively

High expression of claudin-1 protein in papillary thyroid tumor and its regional lymph node metastasis

Claudins, known as major contributors in the formation of the tight junction, are differentially expressed in malignant tumors as compared to the corresponding healthy tissues. Therefore, they are thought to play a role in carcinogenesis and tumor progression. Altered expression of claudin-1 has been reported in several tumor types including endometrial, papillary renal cell and colonic carcinoma, and increased claudin-1 mRNA levels have been observed in papillary thyroid carcinoma (PTC). In this study, we aimed at determining the pattern of claudin-1 expression in various types of thyroid lesions at the protein level and investigating the immunolocalization of β-catenin reported to regulate claudin-1 expression. Samples included 19 PTCs, ten cases of corresponding regional lymph node metastasis, eight papillary microcarcinomas (PMC), 17 follicular thyroid carcinomas (FTC) and 19 follicular adenomas (FA). All cases were evaluated by quantitative immunohistochemistry. Conspicuous claudin-1 immunostaining was detected in the majority of PTC/PMC primary tumors and lymph node metastases (19/27 and 9/10, respectively). On the other hand, we found weak or no claudin-1 expression in any of the FA and FTC cases or peritumoral non-malignant thyroid tissues. Our data prove that high claudin-1 protein expression is specific for PTC and its regional lymph node metastases, while we failed to verify that claudin-1 is regulated by β-catenin in thyroid tumors. Based on these results