Differential pattern of HIF-1α expression in HNSCC cancer stem cells after carbon ion or photon irradiation: one molecular explanation of the oxygen effect
Résumé
Background: Head and neck squamous cell carcinoma (HNSCC) are resistant to standard treatments, partly due to cancer stem cells (CSCs) localised in hypoxic niches. Compared to X-rays, carbon ion irradiation relies on better ballistic properties, higher relative biological effectiveness and the absence of oxygen effect. Hypoxia-inducible factor-1a (HIF-1a) is involved in the resistance to photons, whereas its role in response to carbon ions remains unclear.
Methods:Two HNSCC cell lines and their CSC sub-population were studied in response to photons or carbon ion irradiation, innormoxia or hypoxia, after inhibition or not of HIF-1a.
Results:Under hypoxia, compared to non-CSCs, HIF-1ais expressed earlier in CSCs. A combined effect photons/hypoxia, lessobserved with carbon ions, results in a synergic and earlier HIF-1aexpression in both subpopulations. The diffuse ROS productionby photons is concomitant with HIF-1aexpression and essential to its activation. There is no oxygen effect in response to carbonions and the ROS localised in the track might be insufficient to stabilise HIF-1a. Finally, in hypoxia, cells were sensitised to bothtypes of radiations after HIF-1ainhibition.
Conclusions:Hypoxia-inducible factor-1aplays a main role in the response of CSCs and non-CSCs to carbon ion and photonirradiations, which makes the HIF-1atargeting an attractive therapeutic challenge.
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