会議発表用資料 Role of HIF-1α in the response of HNSCC cancer stem cells after carbon ion exposures

A-S., Wozny  ,  Gersende, ALPHONSE  ,  Vares, G.  ,  藤森, 亮  ,  中島, 徹夫  ,  C., Rodriguez-Lafrasse

2017-04-17
内容記述
Head and neck squamous cell carcinoma (HNSCC) are resistant to standard treatments, partly due to the presence of Cancer Stem Cells (CSCs) localized in hypoxic niches. The protein HIF-1α (Hypoxia-Inducible Factor 1α)is considered as the major transcriptional regulator of the cellular response to oxygen homeostasis. We previously showed that inhibition of HIF-1α lead to the decrease of HNSCC-CSC survival after carbon ion (GANIL, France (75MeV/n)) and photon irradiations in hypoxic conditions. This proposal aimed of clarifying the role of HIF-1α in the response of HNSCC-CSCs. After inhibition of HIF-1α with a siRNA, DNA repair and epithelio-mesenchymal transition(EMT) were studied in response to carbon ion(290MeV/n-SOBP) and photon (250kV) irradiations in normoxic or hypoxic(1% O2) conditions. Radiosentization observed after HIF-1αinhibition is associated with a significant increase of residual DSBs in response to both types of radiation. Furthermore, under hypoxia, HIF-1αinhibition is associated with a low proportion of migrating and invasive cells, confirming the role of HIF-1α in EMT. In summary,HIF-1α participates to radioresistance by increasing cell survival, DNA repair and invasiveness and contributes to tumor escape. These preliminary results will be confirmed during the next beam time.
H28年度HIMAC共同利用研究成果発表会

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