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

作者：Wozny Anne Sophie; Lauret Alexandra; Battiston Montagne Priscillia; Guy Jean Baptiste; Beuve Michael; Cunha Micaela; Saintigny Yannick; Blond Emilie; Magne Nicolas; LaIle Philippe; Ardail Dominique; Alphonse Gersende; Rodriguez Lafrasse Claire

来源：British Journal of Cancer, 2017, 116(10): 1340-1349.

DOI：10.1038/bjc.2017.100

• hypoxia-inducible factor-1 alpha
• HIF-1 alpha
• carbon ion irradiation
• cancer stem cells
• hypoxia
• reactive oxygen species
• oxygen effect
• photon irradiation

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 alpha (HIF-1 alpha) 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-1 alpha.
Results: Under hypoxia, compared to non-CSCs, HIF-1 alpha is expressed earlier in CSCs. A combined effect photons/hypoxia, less observed with carbon ions, results in a synergic and earlier HIF-1 alpha expression in both subpopulations. The diffuse ROS production by photons is concomitant with HIF-1 alpha 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-1 alpha. Finally, in hypoxia, cells were sensitised to both types of radiations after HIF-1 alpha inhibition.
Conclusions: Hypoxia-inducible factor-1 alpha plays a main role in the response of CSCs and non-CSCs to carbon ion and photon irradiations, which makes the HIF-1 alpha targeting an attractive therapeutic challenge.

• 出版日期2017-5-9