Epithelial-mesenchymal-transition Induced by EGFR Activation Interferes With Cell Migration and Response to Irradiation and Cetuximab in Head and Neck Cancer Cells

Radiother Oncol. 2011 Oct;101(1):158-64. doi: 10.1016/j.radonc.2011.05.042. Epub 2011 Jun 12.

Abstract

Background and purpose: The role of epithelial-mesenchymal transition (EMT) in the poor outcome of EGFR-overexpressing SCCHN was evaluated.

Material and methods: SCCHN cell lines were characterized for their cell morphology and expression of EGFR and the EMT-associated factors E-cadherin, vimentin and Snail1. The migratory potential of cells was assessed in motility assays. Response to irradiation and cetuximab was determined using clonogenic survival assays.

Results: High basal expression of E-cadherin but low to absent vimentin expression could be observed in all SCCHN cell lines. Although E-cadherin expression levels did not change after treatment with EGF we observed a significant change in cell morphology resembling EMT. SCCHN cells with high basal levels of Snail1 resulting from constitutive EGFR activation were characterized by mesenchymal-like morphology, elevated migratory potential, reduced sensitivity to irradiation and cetuximab but increased sensitivity to the combined treatment.

Conclusions: Autocrine activation of EGFR leading to EMT is associated with a metastatic phenotype and reduced sensitivity of SCCHN cells to single-modality treatment with cetuximab or irradiation. The potential of Snail1 as biomarker for selection of patients who will mostly benefit from a combination of cetuximab and radiotherapy has to be evaluated in future clinical studies.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal, Humanized
  • Carcinoma, Squamous Cell / therapy*
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Movement / radiation effects*
  • Cetuximab
  • Chemoradiotherapy
  • Epithelial-Mesenchymal Transition / drug effects
  • Epithelial-Mesenchymal Transition / physiology*
  • Epithelial-Mesenchymal Transition / radiation effects
  • ErbB Receptors / metabolism*
  • Flow Cytometry
  • Head and Neck Neoplasms / therapy*
  • Humans
  • Immunoblotting
  • Radiation, Ionizing
  • Real-Time Polymerase Chain Reaction
  • Squamous Cell Carcinoma of Head and Neck

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • ErbB Receptors
  • Cetuximab