| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
The possible involvement of membrane microdomains in oxidative stress-induced change in invasion of hepatoma cells was investigated. I have already reported that reactive oxygen species could promote hepatoma cell invasion and that the autocrine pathway between hepatoyte growth factor (HGF) and its receptor, c-met, is involved in this promotion. In this research, the decrease in the invasive activity under the hypoxia culture condition without changing HGF gene expression was observed, suggesting the presence of the novel regulation pathway in oxidative stress-induced change in hepatoma cell invasion. AH109A cells expressed integrins α2, α5, α6, β1 on their cell membrane and these integrins were proved to be localized in their membrane microdomains. Moreover, methyl-β-cyclodextrin affected AH109A invasion, suggesting the involvement of membrane microdomain in their invasion. So, the effect of oxidative stress, especially hypoxia, on hepatoma cell invasion was extensively investigated. AH109A cells, when cultured under the hypoxia condition, showed decreased invasive activities, but they did not show decreased adhesive activities to the normal cell monolayer and decreased HGF production. The expression level of c-met in AH109A cells did not change under the hypoxia culture condition. Recently the association of c-met with integrins is reported to be important in the promotion of cell motility by HGF. These results suggest that hypoxia may affect the association of c-met with integrins in membrane microdomains of AH109A cells, thus changing their invasive activities. Although further studies, such as co-immunoprecipitation assay of c-met and integrins, are thought to be needed to clarify the precise mechanism for hypoxia-induced reduction in invasive activities, some evidences for the possible involvement of membrane microdomains in oxidative stress-induced change in hapatoma invasion were obtained by this research.
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