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


CONCLUSIONS
Serous adenocarcinomas formed functional TJs in vitro. The presence of claudin-4 might be essential for the function of TJs in ovarian cancer.
Zhu
Yihong
Y
Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy at Göteborg University, Göteborg, Sweden. yihong.zhu@obgyn.gu.se
Sundfeldt
Karin
K
D000230:Adenocarcinoma / Q000378:metabolism / Q000503:physiopathology*; D018262:Adenocarcinoma, Clear Cell / Q000378:metabolism / Q000503:physiopathology; D015820:Cadherins / Q000378:metabolism; D018269:Carcinoma, Endometrioid / Q000378:metabolism / Q000503:physiopathology; D045744:Cell Line, Tumor; D062465:Claudin-3; D062506:Claudin-4; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D010750:Phosphoproteins / Q000378:metabolism; D019108:Tight Junctions / Q000502:physiology*; D062826:Zonula Occludens-1 Protein
C568122:CLDN3 protein, human; C568157:CLDN4 protein, human; D015820:Cadherins; D062465:Claudin-3; D062506:Claudin-4; D008565:Membrane Proteins; D010750:Phosphoproteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein