title: Differences in expression patterns of the tight junction proteins,claudin 1, 3, 4 and 5, in human ovarian surface epithelium as compared to epithelia in inclusion cysts and epithelial ovarian tumours.
abstract: Human ovarian surface epithelium (OSE), regarded as the precursor cell of epithelial ovarian adenocarcinoma, is not a fully developed epithelium when situated on the ovarian surface. It lacks epithelial characteristics such as the cell-cell adhesion factor epithelial (E)-cadherin, but as we have shown earlier, this OSE can form functional tight junctions (TJs) in culture. Recent gene-expression data on ovarian adenocarcinoma has pointed out a family of TJ proteins, the claudins, to be highly expressed in malignant compared to benign ovarian tumours. The purpose of this study was to investigate the distribution of claudin 1-5 proteins in cultured OSE (n=4), normal ovarian (n=11), benign (n=8), borderline (n=7) and ovarian cancer (n=22) tissues. We found that a weak or absence of expression of claudin 3 and claudin 4 in surface OSE changed to typical cell-border localisation in OSE of inclusion cysts in the normal ovarian stroma. Semiquantitative estimations of immunoblots showed that claudin 3 was significantly increased in ovarian adenocarcinomas compared to benign and borderline-type tumours. Claudin 4 was significantly increased in both borderline-type and ovarian adenocarcinomas compared to benign tumours, whereas no changes were found for claudin 1 or 5. Concerning relation to Federation for International Gynaecology and Obstetrics (FIGO) grade, claudin 3, but not claudin 4, was significantly increased in moderately, poorly and undifferentiated adenocarcinomas compared to well-differentiated and borderline-type tumours. No significant changes were noticed for any claudin with regard to FIGO stages. We conclude that both claudin 3 and 4, even though they differ in expression during ovarian malignant transformation, might be used as novel markers for ovarian tumours. The observations of lack of claudin 4 and low expression of claudin 3 in OSE strengthen our current knowledge about the biological nature of these cells as an undeveloped epithelium.
authors.affiliation: Department of Obstetrics/Gynaecology, The Sahlgrenska Academy at Göteborg University, S-413 45 Göteborg, Sweden.
authors.forename: Yihong
authors.initials: Y
authors.lastname: Zhu
authors.forename: Mats
authors.initials: M
authors.lastname: Brännström
authors.forename: P-O
authors.initials: PO
authors.lastname: Janson
authors.forename: Karin
authors.initials: K
authors.lastname: Sundfeldt
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis; D002471:Cell Transformation, Neoplastic; D062445:Claudin-1; D062465:Claudin-3; D062506:Claudin-4; D062507:Claudin-5; D004848:Epithelium; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D015151:Immunoblotting; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D010048:Ovarian Cysts / Q000235:genetics* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D010053:Ovary / Q000502:physiology; D010641:Phenotype; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; C568108:CLDN1 protein, human; C568122:CLDN3 protein, human; C568157:CLDN4 protein, human; C107466:CLDN5 protein, human; D062445:Claudin-1; D062465:Claudin-3; D062506:Claudin-4; D062507:Claudin-5; D008565:Membrane Proteins