title: Epidermal growth factor is a potential biomarker for poor cetuximab response in tongue cancer cells.
abstract: BACKGROUND
  Head and neck squamous cell carcinoma is frequently associated with aberrant epidermal growth factor receptor (EGFR) signaling, which contributes to tumor growth. Here, the functional importance of EGFR ligands in relation to proliferation and sensitivity to the EGFR-targeted therapy cetuximab was investigated in three tongue cancer cell lines.
  
  
  METHODS
  The influence of epidermal growth factor (EGF), amphiregulin (AR), and epiregulin (EPR) on tumor cell proliferation and cetuximab response was evaluated by the addition of recombinant human (rh) proteins or by siRNA-mediated downregulation of the endogenous ligand production. The expression, activation and cellular distribution of EGFR were assessed by Western blot analysis and immunocytochemistry.
  
  
  RESULTS
  EGF downregulation suppressed the proliferation of all investigated tumor cell lines, whereas the response to an increased level of EGF differed between EGFR-overexpressing and EGFR-non-overexpressing cell lines. Furthermore, tumor cells consistently displayed increased cetuximab resistance upon the addition of rhEGF, whereas EGF silencing was associated with an improved cetuximab response. The data regarding AR and EPR were inconclusive.
  
  
  CONCLUSIONS
  Our data suggest that the amount of EGF is a determinant of the tumor cell proliferation rate and the response to cetuximab treatment in tongue cancer. Thus, EGF is a potential predictive biomarker of poor cetuximab response and a possible treatment target.
authors: 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: Anna
authors: A
authors: Ansell
authors: 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: Adam
authors: A
authors: Jedlinski
authors: 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: Ann-Charlotte
authors: AC
authors: Johansson
authors: 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: Karin
authors: K
authors: Roberg
mesh_terms: D066258:Amphiregulin / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000032:analysis / Q000096:biosynthesis*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000068818:Cetuximab / Q000494:pharmacology*; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D004815:Epidermal Growth Factor / Q000032:analysis / Q000096:biosynthesis*; D066260:Epiregulin / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology; D066246:ErbB Receptors / Q000096:biosynthesis / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008024:Ligands; D058990:Molecular Targeted Therapy; D000077195:Squamous Cell Carcinoma of Head and Neck; D014062:Tongue Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology
chemical_list: D066258:Amphiregulin; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D066260:Epiregulin; D008024:Ligands; D004815:Epidermal Growth Factor; C512478:EGFR protein, human; D066246:ErbB Receptors; D000068818:Cetuximab
keywords: epidermal growth factor receptor ligands; erbitux; head and neck cancer; tongue cancer; treatment response