title: The relationship between EMT, CD44high/EGFRlowphenotype, and treatment response in head and neck cancer cell lines.
abstract: BACKGROUND
  Head and neck squamous cell carcinoma (HNSCC) tumors are often therapy resistant and may originate from cancer stem cells or tumor cells with an epithelial-to-mesenchymal transition (EMT) phenotype. The aim of this study was to characterize HNSCC cell lines with regard to EMT profile and to investigate the influence of EMT on the response to treatment.
  
  
  METHODS
  mRNA expression of the EMT-associated genes CDH1 (E-cadherin), CDH2 (N-cadherin), FOXC2, TWIST1, VIM (vimentin), and FN1 (fibronectin) was determined using quantitative real-time PCR. Cell morphology and migration were investigated by phase-contrast microscopy and Boyden chamber assay, respectively. The cell surface expression of CD44 and epidermal growth factor receptor (EGFR) was examined by flow cytometry. The response to radiotherapy, cetuximab, and dasatinib was assessed by crystal violet staining.
  
  
  RESULTS
  A total of 25 cell lines investigated differed greatly with regard to EMT phenotype. Cell lines with an EMT expression profile showed a mesenchymal morphology and a high migratory capacity. In addition, they exhibited a high cell surface expression of CD44 and a low expression of EGFR, a pattern previously associated with stemness. When the EMT inducer transforming growth factor-β (TGF-β) was added to non-EMT cells, changes in treatment responses were observed. Moreover, the expression of TWIST1 was found to correlate with radioresistance.
  
  
  CONCLUSIONS
  The data presented in this report suggest that EMT is associated with a CD44high/EGFRlowphenotype and possibly negative impact on radiotherapy response in HNSCC cell lines.
authors.affiliation: Division of Oto-Rhino-Laryngology and Head and Neck Surgery, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Ann-Charlotte
authors.initials: AC
authors.lastname: Johansson
authors.affiliation: Division of Oto-Rhino-Laryngology and Head and Neck Surgery, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.|Department of ENT-Head and Neck Surgery UHL, County Council of Östergötland, Linköping, Sweden.
authors.forename: Linnea
authors.initials: L
authors.lastname: La Fleur
authors.affiliation: Division of Oto-Rhino-Laryngology and Head and Neck Surgery, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.|Department of ENT-Head and Neck Surgery UHL, County Council of Östergötland, Linköping, Sweden.
authors.forename: Styliani
authors.initials: S
authors.lastname: Melissaridou
authors.affiliation: Division of Oto-Rhino-Laryngology and Head and Neck Surgery, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden. karin.roberg@liu.se.|Department of ENT-Head and Neck Surgery UHL, County Council of Östergötland, Linköping, Sweden. karin.roberg@liu.se.
authors.forename: Karin
authors.initials: K
authors.lastname: Roberg
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D066246:ErbB Receptors / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D010641:Phenotype; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D011878:Radiotherapy; D051879:Twist-Related Protein 1 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D009687:Nuclear Proteins; D012333:RNA, Messenger; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; D066246:ErbB Receptors
keywords: CD44; Twist1; dasatinib; epithelial-to-mesenchymal transition; radiation