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

Int J Cancer. 2006 Apr 15;118(8):1884-91. doi: 10.1002/ijc.21506.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Biomarkers, Tumor / analysis
  • Cell Transformation, Neoplastic
  • Claudin-1
  • Claudin-3
  • Claudin-4
  • Claudin-5
  • Epithelium
  • Female
  • Gene Expression Profiling
  • Humans
  • Immunoblotting
  • Membrane Proteins / biosynthesis*
  • Membrane Proteins / genetics
  • Ovarian Cysts / genetics*
  • Ovarian Cysts / pathology
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Ovary / physiology
  • Phenotype
  • Tumor Cells, Cultured


  • Biomarkers, Tumor
  • CLDN1 protein, human
  • CLDN3 protein, human
  • CLDN4 protein, human
  • CLDN5 protein, human
  • Claudin-1
  • Claudin-3
  • Claudin-4
  • Claudin-5
  • Membrane Proteins