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.
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.
Authors: Emiliano Cocco; Erik M Shapiro; Sara Gasparrini; Salvatore Lopez; Carlton L Schwab; Stefania Bellone; Ileana Bortolomai; Natalia J Sumi; Elena Bonazzoli; Roberta Nicoletti; Yang Deng; W Mark Saltzman; Caroline J Zeiss; Floriana Centritto; Jonathan D Black; Dan-Arin Silasi; Elena Ratner; Masoud Azodi; Thomas J Rutherford; Peter E Schwartz; Sergio Pecorelli; Alessandro D Santin Journal: Int J Cancer Date: 2015-08-18 Impact factor: 7.396
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Authors: Jonathan D Black; Salvatore Lopez; Emiliano Cocco; Carlton L Schwab; Diana P English; Alessandro D Santin Journal: Toxins (Basel) Date: 2015-04-01 Impact factor: 4.546