Differential pattern of HIF-1? expression in HNSCC cancer stem cells after carbon ion or photon irradiation: one molecular explanation of the oxygen effect.

ABSTRACT:

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? (HIF-1?) 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?.

Results

Under hypoxia, compared to non-CSCs, HIF-1? is expressed earlier in CSCs. A combined effect photons/hypoxia, less observed with carbon ions, results in a synergic and earlier HIF-1? expression in both subpopulations. The diffuse ROS production by photons is concomitant with HIF-1? 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?. Finally, in hypoxia, cells were sensitised to both types of radiations after HIF-1? inhibition.

Conclusions

Hypoxia-inducible factor-1? plays a main role in the response of CSCs and non-CSCs to carbon ion and photon irradiations, which makes the HIF-1? targeting an attractive therapeutic challenge.

SUBMITTER: Wozny AS 

PROVIDER: S-EPMC5482725 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature