Syracuse

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

Wozny, Anne-Sophie | Lauret, Alexandra | Saintigny, Yannick | Battiston-Montagne, Priscillia | Beuve, Michaël | Alphonse, Gersende | Rodriguez-Lafrasse, Claire

Edité par CCSD -

International audience. 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

• Description
• Sujet/Public
• Outil
• Outil d'anticipation
• Mémoire et thèse
• Gestion