Claudin-4: a potential therapeutic target in chemotherapy-resistant ovarian cancer

Anticancer Res. 2011 Apr;31(4):1271-7.

Abstract

Background: Claudin-4, a component of the tight junction, plays an important role in tumorigenesis and metastasis of ovarian cancer, but its role in platinum resistance has not been elucidated.

Materials and methods: Claudin-4 expression in ovarian cancer cells was inhibited and the changes in cisplatin sensitivity were examined. Fluorescence-labeled cisplatin was used to examine whether inhibition of claudin-4 changed the cellular accumulation of cisplatin. Claudin-4 expression in ovarian cancer tissue resected from the patients surgically was evaluated immunohistochemically.

Results: Suppression of claudin-4 resulted in a significant increase of cisplatin sensitivity and cellular accumulation of fluorescence-labeled cisplatin. Claudin-4 expression was significantly greater in ovarian cancer tissue from chemoresistant patients compared to chemosensitive patients. The overall survival was significantly shorter for claudin-4-positive than claudin-4-negative cases.

Conclusion: These data suggest that claudin-4 contributes to platinum resistance in ovarian cancer and may be a potential target in the treatment of platinum-resistant tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Clear Cell / drug therapy
  • Adenocarcinoma, Clear Cell / metabolism
  • Adenocarcinoma, Clear Cell / pathology
  • Adenocarcinoma, Mucinous / drug therapy
  • Adenocarcinoma, Mucinous / metabolism
  • Adenocarcinoma, Mucinous / pathology
  • Antineoplastic Agents / therapeutic use*
  • Cell Line, Tumor
  • Cisplatin / therapeutic use*
  • Claudin-4
  • Cystadenocarcinoma, Serous / drug therapy
  • Cystadenocarcinoma, Serous / metabolism
  • Cystadenocarcinoma, Serous / pathology
  • Drug Resistance, Neoplasm*
  • Endometrial Neoplasms / drug therapy
  • Endometrial Neoplasms / metabolism
  • Endometrial Neoplasms / pathology
  • Female
  • Fluorescent Antibody Technique
  • Humans
  • Immunoenzyme Techniques
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Survival Rate
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • CLDN4 protein, human
  • Claudin-4
  • Membrane Proteins
  • Cisplatin