Essential role of HIF-1α in both resistance to photon and carbon ion exposures and invasiveness of Head and Neck Squamous Cell Carcinoma (HNSCC) cancer stem cells - Archive ouverte HAL Accéder directement au contenu
Communication Dans Un Congrès Année : 2016

Essential role of HIF-1α in both resistance to photon and carbon ion exposures and invasiveness of Head and Neck Squamous Cell Carcinoma (HNSCC) cancer stem cells

Résumé

Purpose: HNSCC have a poor prognosis, which is partly due to the presence of cancer stem cells (CSCs) resistant to chemo- and radio-therapies. CSCs are located in a hypoxic environment which leads to HIF-1a stabilization and induces epithelial mesenchymal transition. Reactive Oxygen Species (ROS), produced in response to hypoxia and/or irradiation, play a key role in this stabilization. However, mechanisms leading to HIF-1a stabilization and their consequences on the invasiveness need to be clarified in CSCs exposed to carbon or photon radiation in hypoxia. Methods: Two HNSCC cells lines and their CSCs, sorted by flow cytometry, were grown under normoxia or hypoxia (1% O2). Oxygen Enhancement Ratio (OER) was calculated at 10% survival after photon and carbon ion (75MeV/n) irradiation. The expression of HIF-1a was followed by Western-Blots. ROS were quantified with a CM-H2DCFDA dye and Migration/Invasion with Boyden chambers. Results: Both parental and CSCs sub-populations are more resistant to photons under hypoxia (OER>1.2) whereas the oxygen effect is canceled after carbon ion exposure (OER=1). Interestingly, as for the OER values, HIF-1a expression is function of the type of irradiation, stabilized with photons and fully inhibited with carbon ions. Additionally, under hypoxia, HIF-1a appears earlier in CSCs than in non-CSCs, and is correlated with ROS levels, confirming their adaptive properties to hypoxia. Finally, the invasion/migration abilities of CSCs are more important than in non-CSCs under normoxia, and that, even more significantly under hypoxia. After carbon ion exposure, in both conditions of oxygenation, invasion/migration processes are decreased compared with photons. Conclusion: HIF-1a plays a key role in the radioresistance and the invasiveness of CSCs. No expression of HIF-1a was found after carbon ion exposure suggesting that hadrontherapy could be a relevant alternative to kill CSCs. Supported by ANR-11-LABX-0063, ANR-11-INBS-0007, INCa-DGOS-4664

Domaines

Cancer
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Dates et versions

hal-01277916 , version 1 (23-02-2016)

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  • HAL Id : hal-01277916 , version 1

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Anne-Sophie Wozny, Alexandra Lauret, Yannick Saintigny, Priscillia Battiston-Montagne, Michaël Beuve, et al.. Essential role of HIF-1α in both resistance to photon and carbon ion exposures and invasiveness of Head and Neck Squamous Cell Carcinoma (HNSCC) cancer stem cells. Forum de la recherche en cancérologie Rhône-Alpes Auvergne, Mar 2016, Lyon, France. ⟨hal-01277916⟩
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