T-cadherin in epithelial ovarian cancer: relationship with cancer progression and drug resistanceT-cadherin in epithelial ovarian cancer: relationship with cancer progression and drug resistance

Abstract Background: T-cadherin plays a crucial role in maintaining normal tissue structure by regulating specific cell adhesion, cellular recognition and signal transduction. The purpose of this study was to evaluate whether T-cadherin influences epithelial ovarian cancer (EOC) progression, differentiation and drug resistance and its possible mechanisms. Methods: Epithelial ovarian carcinoma (EOC, n=63) and relevant contralateral normal ovarian (CNO, n=41) fresh tissues were collected from epithelial ovarian carcinoma patients, and benign ovarian tumour fresh tissues were collected from 55 patients with benign ovarian tumours. The human epithelial ovarian carcinoma cell line A2780 was cultured. T-cadherin expression was assessed by real-time RT-PCR and Western blotting, and the expression of matrix metalloproteinase-2 (MMP-2) was detected by Western blotting. pcDNA‑T‑cad plasmid technology was used to upregulate T-cadherin expression. In addition, A2780 cell migration and invasion ability, viability, colony formation, proliferation, apoptosis and sensitivity to paclitaxel were measured. Results: T‑cadherin mRNA and protein expression in EOC tissues from EOC patients was significantly downregulated, and there was no significant difference between the matched contralateral normal ovarian fresh tissue from the same patient and the benign ovarian tumour tissues from other patients. The migration and invasion abilities, viability, colony formation, and proliferation were attenuated by restoration of T‑cadherin expression in A2780 cells via pcDNA‑T‑cad transfection; apoptosis, MMP-2 expression and sensitivity to Taxol were also enhanced by restored T‑cadherin expression. The T‑cadherin expression level was well correlated with the clinical characteristics and symptoms of EOC patients, including tumour stage, histology, lymph node metastasis, tumour size, distant metastasis and cisplatin resistance. Conclusions: T‑cadherin participates in the processes of epithelial ovarian carcinoma cell migration, invasion, proliferation, apoptosis and sensitivity to paclitaxel and can regulate the expression of MMP-2. Downregulation of T‑cadherin expression may contribute to epithelial ovarian cancer progression, differentiation and drug resistance.