Abstract 2411: The epithelial-mesenchymal transition of gastric cancer cells was stimulated by TGFβR signaling in hypoxia

Abstract

Abstract Introduction: Epithelial mesenchymal transition (EMT) is a cellular process during which epithelial cells acquire mesenchymal properties while losing cell-cell interactions and apicobasal polarity. EMT is considered to be correlated with malignancy of cancer cells and responsible for cancer invasion and metastasis. Patients with gastric cancer show a poor prognosis because of frequent metastasis. We previously reported that distant metastasis was associated with hypoxia in gastric cancer. Therefore, we investigated the effect of hypoxic condition on EMT of gastric cancer cells. Materials and Methods:Seven gastric cancer cell lines derived from gastric cancer were used. Cells were cultured in normoxia (21% O2) or hypoxia (1% O2) for 24h. EMT rate was evaluated as the percentage of spindle-shaped cells of total cells. The expression level of TGFβ and TGFβ receptor was evaluated by real time RT-PCR. Effect of several inhibitors on the EMT was evaluated by cell morphology. The TGFβ1 level of the cell culture supernate was measured by a quantitative sandwich enzyme immunoassay technique. Results: Hypoxia stimulated EMT of OCUM-2MD3 and OCUM-12 cells, but not that of other cell lines. The level of TGFβ expression was increased significantly (p<0.01) under hypoxia in comparison with normoxia. The level of TGFβ receptor expression was increased in OCUM-2MD3 cells, but not OCUM-2M cells. TGFβR inhibitor, SB431542, significantly suppressed EMT of OCUM-2MD3 (p=0.03) and OCUM-12 (p<0.01). In OCUM-2MD3 and OCUM-12, the quantity of TGFβ1 in cell culture supernatant significantly increased under hypoxia compared to normoxia, but not OCUM-2Mcells. Conclusion: Hypoxia stimulates the EMT of gastric cancer cells via TGFβ/ TGFβ receptor signaling. TGFβ receptor inhibitor might be promising for the treatment of metastasis of gastric cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2411. doi:1538-7445.AM2012-2411