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

• Published in: British journal of cancer Vol. 116; no. 10; p. 1340
• Main Authors: Wozny, Anne-sophie, Lauret, Alexandra, Battiston-montagne, Priscillia, Guy, Jean-baptiste, Beuve, Michael, Cunha, Micaela, Saintigny, Yannick, Blond, Emilie, Magne, Nicolas, Lalle, Philippe, Ardail, Dominique, Alphonse, Gersende, Rodriguez-lafrasse, Claire
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 09-05-2017
• Subjects: Cancer therapies; Carbon; Hypoxia; Proteins; Radiation therapy; Stem cells; Tumors; France
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2017.100

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-1α (HIF-1α) 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, in normoxia or hypoxia, after inhibition or not of HIF-1α.Results: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: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.