Abstract 2057: Hypoxia stimulates the epithelial-mesenchymal transition of gastric cancer cells via TGF-β/ TGF-β receptor signaling

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 to be responsible for cancer invasion and metastasis. Patients with gastric cancer show a poor prognosis because of frequent metastasis. We previously reported that hypoxia was associated with distant metastasis and poor prognosis in gastric cancer. Therefore, we investigated the effect of hypoxic condition on EMT of gastric cancer cells. Materials and Methods:Three gastric cancer cell lines, OCUM-2MD3, OCUM-2M, and OCUM-12 derived from gastric cancer were used. Cells were cultured in normoxia (21% O2) or hypoxia (1% O2). EMT rate was evaluated as the percentage of spindle-shaped cells of total cells. The expression level of TGF-β and TGF-β receptor was evaluated by real time RT-PCR. Effect of TGF-β or TGF-βR inhibitor, SB431542, on the EMT was evaluated by cell morphology. Results: Hypoxia stimulated EMT of OCUM-2MD3 and OCUM-12 cells, but not that of OCUM-2M cells. The level of TGF-β expression was increased significantly (p<0.001) under hypoxia in comparison with normoxia in all of three cell lines. The level of TGF-β receptor expression was increased in OCUM-2MD3 and OCUM-12 cells, but not OCUM-2M cells. TGF-βR inhibitor, SB431542, significantly suppressed EMT of OCUM-2MD3 (p=0.03) and OCUM-12 (p<0.01). Conclusion: Hypoxia stimulates the EMT of gastric cancer cells via TGF-β/ TGF-β receptor signaling. TGF-β receptor inhibitor might be promising for the treatment of gastric cancer. 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 2057. doi:10.1158/1538-7445.AM2011-2057