Tight junction formation in epithelial ovarian adenocarcinoma

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.

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.

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 Ca(2+) switch experiments, functional TJs were shown to build up only in serous adenocarcinomas.

Serous adenocarcinomas formed functional TJs in vitro. The presence of claudin-4 might be essential for the function of TJs in ovarian cancer.