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

Oncotarget. 2016 Jul 26;7(30):47738-47749. doi: 10.18632/oncotarget.10281.

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: EGFRLow, 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.

Keywords: HNSCC; cancer stem cells; carbon ion irradiation; invasion; migration.

MeSH terms

  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / pathology*
  • Carcinoma, Squamous Cell / radiotherapy*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / radiation effects
  • Cell Proliferation / drug effects
  • Cell Proliferation / radiation effects
  • Cetuximab / pharmacology
  • Chemoradiotherapy
  • Epithelial-Mesenchymal Transition
  • ErbB Receptors / biosynthesis
  • Head and Neck Neoplasms / drug therapy
  • Head and Neck Neoplasms / pathology*
  • Head and Neck Neoplasms / radiotherapy*
  • Heavy Ion Radiotherapy
  • Humans
  • Neoplasm Invasiveness
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / pathology*
  • Neoplastic Stem Cells / radiation effects*
  • Photons / therapeutic use
  • Squamous Cell Carcinoma of Head and Neck
  • Survival Analysis

Substances

  • EGFR protein, human
  • ErbB Receptors
  • Cetuximab