Abstract 3363: Iron deficiency suppress EMT through downregulation of N-cadherin in esophageal cancer

Abstract

Abstract [Introduction] Epithelial-Mesenchymal-transition(EMT) plays a great roles in cancer metastasis and invasion.Mecanism of EMT remains controversial, but it is recognized that some protein change their expression, including E-cadherin and N-cadherin.It is reported that downregulation of N-cadherin reduce cancer metastasis and invasiveness. Iron metabolism and its relationship with cancer cell were studied for a long time. Iron overload is known to induce some kinds of cancer, which suggests that prevention of iron overload is a therapeutic strategy of cancer prevention. Iron deficiency is also known to suppress the tumor growth in vivo study. But the efficacy is not superior to the ordinary chemotherapy, it's not a standard therapeutic strategy of cancer. Recently, it is reported that iro metabolism is essential for EMT, and iron defficiency downregulate EMT change. In this study, we demonstrated that iron deficiency downregulate the expression of the EMT protein, N-cadherin, and suppressed the ability of metastasis and invasiveness. This result suggests that Iron controlled treatment can be novel therapeutic agent for cancer under EMT. [Matherials and Methods] TE-1,TE-4,TE-8 and TE-10 esophageal squamous cell carcinoma, OE19 and OE33 esophageal adenocarcinoma cell lines were used in this study. In vitro study, cell viability was determined by XTT assay. Iron chelator deferasirox was prepared in vitro study to make iron deficient condition. To determine that iron deficiency suppresses EMT and invasiveness of cancer cell line, western blotting analysis, the three-dimensional spheroid model analysis and migration assay were done. In vivo study, Normal diet and Iron deficient diet were fed for 3 weeks before implantation of TE-4 cells in athymic male nude mice(n=8/group). After implantation, each diet was fed continually. [Results]Deferasirox reduces proliferation of all cell line in a concentration manner. According to western blotting analysis, deferasirox induces reduction of N-cadherin protein in TE-4 and TE-10 cell lines. N-cadherin downregulation declines invasiveness of TE-4 and TE-10 cell lines in the three-dimensional spheroid model analysis and migration assay. In vivo study, tumor growth was suppressed in iron deficient diet group (tumor volume: normal diet vs iron deficient diet = 30.7±1.1 vs 10.9±2.2) [Conclusion]Iron controlled treatment can be novel therapeutic agent for invasiveness of cancer under EMT. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3363. doi:10.1158/1538-7445.AM2011-3363