Carbon ion irradiation withstands cancer stem cells' migration/invasion process in Head and Neck Squamous Cell Carcinoma (HNSCC)

// Coralie Moncharmont 1, 2, 3, * , Jean-Baptiste Guy 1, 2, 3, * , Anne-Sophie Wozny 1, 2, 4 , Marion Gilormini 1, 2 , Priscilla Battiston-Montagne 1, 2 , Dominique Ardail 1, 2, 4 , Michael Beuve 5 , Gersende Alphonse 2, 4 , Xavier Simoëns 6 , Chloé Rancoule 3 , Claire Rodriguez-Lafrasse 1, 2, 4, * , Nicolas Magné 1, 2, 3, * 1 Université Lyon 1, Faculté de Médecine-Lyon-Sud, Oullins, 69921, France 2 Laboratoire de Radiobiologie Cellulaire et Moléculaire, Institut de Physique Nucléaire de Lyon, IPNL, Villeurbanne, 69622, France 3 Département de Radiothérapie, Institut de Cancérologie de la Loire - Lucien Neuwirth, St Priest en Jarez, 42270, France 4 Hospices Civils de Lyon, Lyon, 69229, France 5 Institut de Physique Nucléaire de Lyon, IPNL, Villeurbanne, 69622, France 6 Département de Pharmacologie Clinique et d’Innovation, Institut de Cancérologie de la Loire - Lucien Neuwirth, St Priest en Jarez, 42270, France * These authors contributed equally to this work Correspondence to: Nicolas Magné, email: nicolas.magne@icloire.fr Keywords: carbon ion irradiation, cancer stem cells, migration, invasion, HNSCC Received: January 24, 2016 Accepted: May 28, 2016 Published: June 24, 2016 ABSTRACT Cancer Stem Cells (CSCs) in Head and Neck Squamous Cell Carcinoma (HNSCC) have extremely aggressive profile (high migratory and invasive potential). These characteristics can explain their resistance to conventional treatment. Efficacy of photon and carbon ion irradiation with addition of cetuximab (5 nM) is studied on clonogenic death, migration and invasion of two HNSCC populations: SQ20B and SQ20B/CSCs. SQ20B express E-cadherin and overexpress EGFR while SQ20B/CSCs express N-cadherin and low EGFR. Cetuximab strongly inhibits SQ20B proliferation but has no effect on SQ20B/CSCs. 2 Gy photon irradiation enhances migration and invasiveness in both populations ( p < 0.05), while cetuximab only stops SQ20B migration ( p < 0.005). Carbon irradiation significantly inhibits invasion in both populations ( p < 0.05), and the association with cetuximab significantly inhibits invasion in both populations ( p < 0.005). These results highlight CSCs characteristics: EGFR Low , cetuximab-resistant, and highly migratory. Carbon ion irradiation appears to be a very promising therapeutic modality counteracting migration/invasion process in both parental cells and CSCs in contrast to photon irradiation.