Differential pattern of HIF-1[alpha] expression in HNSCC cancer stem cells after carbon ion or photon irradiation : one molecular explanation of the oxygen effect
Menée à l'aide de deux lignées cellulaires de carcinome épidermoïde de la tête et du cou, cette étude analyse le rôle du facteur HIF-1alpha dans la réponse des cellules souches cancéreuses aux irradiations par ions carbone ou photons
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-1
α (HIF-1α) is involved in the resistance to photons, whereas its role in response to carbon ions remains unclear. Methods
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Two HNSCC cell lines and their CSC sub-population were studied in response to photons or carbon ion irradiation, in normoxia or hypoxia, after inhibition or not of HIF-1α. Results
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Under hypoxia, compared to non-CSCs, HIF-1α is expressed earlier in CSCs. A combined effect photons/hypoxia, less observed with carbon ions, results in a synergic and earlier HIF-1α expression in both subpopulations. The diffuse ROS production by photons is concomitant with HIF-1α expression and essential to its activation. There is no oxygen effect in response to carbon ions and the ROS localised in the track might be insufficient to stabilise HIF-1α. Finally, in hypoxia, cells were sensitised to both types of radiations after HIF-1α inhibition. Conclusions
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Hypoxia-inducible factor-1α plays a main role in the response of CSCs and non-CSCs to carbon ion and photon irradiations, which makes the HIF-1α targeting an attractive therapeutic challenge.