Tight junction formation in epithelial ovarian adenocarcinoma

Background. Epithelial cells are characterised by their ability to form polarised cell sheets with barriers between two tissue compartments. Epithelial tightness and apical/basolateral orientation are maintained through adherens and tight junctions ( TJs). Alterations in junction formation and function could promote tumorigenesis via increased access to growth factors and cytokines. The etiology and development of epithelial ovarian cancer ( EOC) are far from understood. The ovarian surface epithelium ( OSE), regarded as progenitor cells of EOC, form weak functional TJs in culture without expressing typical junction proteins. However, these integral membrane epithelial proteins, E-cadherin, claudin-3 and claudin-4, are often found in EOC. Methods. To clarify whether EOC can form functional TJs, 4 different ovarian cancer cell lines of various histology were analysed for their expression of TJ ( claudin-1, claudin-3, claudin-4 and zonola occludens-1 ( ZO-1)) and adherens junction ( AJ) ( E-cadherin and N-cadherin) proteins, and the ability to build up trans-epithelial resistance ( TER) in culture was measured. Results. We found expression for all cell-junction proteins with a typical honeycomb-staining pattern in the serous adenocarcinomas indicating proper junction formation. Clear-cell and endometrioid adenocarcinomas showed a different expression pattern. By measuring TER, including Ca2+ switch experiments, functional TJs were shown to build up only in serous adenocarcinomas. Conclusion. Serous adenocarcinomas formed functional TJs in vitro. The presence of claudin-4 might be essential for the function of TJs in ovarian cancer.