Authors: ZhiFeng Miao TingTing Zhao ZhenNing Wang YingYing Xu XiaoYun Mao JianHua Wu XingYu Liu Hao Xu Yi You HuiMian Xu
Publish Date: 2014/04/12
Volume: 35, Issue: 7, Pages: 6801-6808
Abstract
Gastric cancers are one of the most common gastrointestinal tumors with proclivity to metastasis Hypoxia is an important feature in solid tumor microenvironment accumulating evidence suggests that chronic and repetitive exposure to hypoxia and reoxygenation seems to provide an advantage to tumor growth However mechanisms of intermittent hypoxia regulating gastric cancer metastatic potential remain to be elucidated In the present study we established the continuous and intermittent gastric cancer hypoxia models and we compared the effects of these models on gastric cancer cell metastatic potential Hypoxiainducible factor1α HIF1α and hypoxia target protein/genes expression in response to different hypoxia models were analyzed by Western blot immunofluorescence and realtime PCR assays Gastric cancer cell migration and invasion ability were analyzed by wound healing and Boyden chamber assay Colony formation and tumor spheroid formation assays were used to assess the ability of selfrenewal Stemrelated protein OCT4 and HIF1α expression were also analyzed by confocal immunofluorescence in single tertiary generation spheroid We demonstrated that the intermittent hypoxia model upregulated expression of both HIF1α and hypoxia target protein/genes in a timedependent manner compared with that of SGC7901 cells cultured under normoxia Remarkably HIF1α protein was more prone to being located in the nucleus of SGC7901 cells under conditions of intermittent hypoxia Gastric cancer cells’ migration and invasion ability were significantly enhanced after hypoxic culture moreover intermittent hypoxiaconditioned SGC7901 cells exhibited higher invasiveness than the continuous hypoxiaconditioned SGC7901 cells Gastric cancer stem/progenitor cell subpopulation was also enlarged which indicated an enhanced selfrenewal ability in hypoxic cultured SGC7901 cells Our study emphasizes the significance of hypoxia in regulating gastric cancer cell metastasis potential Compared with continuous hypoxia intermittent hypoxia is a more effective and potent hypoxic stimulus These results provide a new insight to investigate the hypoxic microenvironment within solid tumors
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