Introduction:Patients with gastric carcinoma show a poor survival because of the frequent metastasis to peritoneum. Hypoxia in tumor has reported to be associated with the metastatic ability of gastric cancer cells. However the mechanisms responsible for the high metastatic potential of hypoxic cancer cells remain unclear. The aim of the current study is to clarify the effect of hypoxic conditions on the peritoneal metastatic ability of gastric cancer cells. Materials and Methods: Three human gastric cancer cell lines, OCUM-2MD3, OCUM-8, and KATO-\#921;\#921;\#921;, were used. Cancer cells were incubated under the hypoxic condition (1% oxygen) or the normoxic condition (21% oxygen) for 48 hours. Adhesion ability of cancer cells to peritoneal components, including fibronectin, laminin, and matrigel, were examined under normoxia or hypoxia by adhesion assay. The expression level of HIF1\#945;, TGF\#946;1, integrins mRNA of cancer cells was examined by RT-PCR. The effect of TGF\#946;-receptor inhibitor, A-77, on the adhesion ability of hypoxic cancer cells was also examined by adhesion assay. Results:The binding abilities of cancer cells to fibronectin, laminin, and matrigel, were significantly increased under hypoxic condition in all three gastric cancer cell lines, OCUM-2MD3, OCUM-8 and KATO-III, compared with those under normoxia. \#945;2-, \#945;3-, and \#945;5-integrin expressions of all of cancer cell lines were increased under hypoxic condition, in comparison with those under normoxic condition. TGF\#946;1 expression of all of cancer cell lines under hypoxic condition was 1.9 fold, 1.7 fold and 16.0 fold higher than that of cells under normoxic condition, while no remarkable change of HIF1\#945; expression was found. TGF\#946; increased \#945;2-, \#945;3-, and \#945;5-integrin expressions of three cancer cell lines. TGF\#946;-receptor inhibitor, A-77, significantly decreased the adhesion ability of hypoxic OCUM-2MD3 cells to fibronectin, laminin, and matrigel, in comparison with the control. Conclusion: Hypoxic conditions promote the adhesion ability of gastric cancer cells to peritoneum. The up-regulation of integrin by TGF\#946;1 under hypoxia might be one of the mechanisms responsible for the high metastatic potential of hypoxic gastric cancer cells to peritoneum.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 241.

100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

American Association for Cancer Research
2009