title: Cetuximab sensitivity of head and neck squamous cell carcinoma xenografts is associated with treatment-induced reduction in EGFR, pEGFR, and pSrc.
abstract: BACKGROUND
  The aims of this study were to validate in vitro drug sensitivity testing of head and neck squamous cell carcinoma (HNSCC) cell lines in an in vivo xenograft model and to identify treatment-induced changes in the epidermal growth factor receptor (EGFR) signaling pathway that could be used as markers for cetuximab treatment response.
  
  
  METHODS
  The in vitro and in vivo cetuximab sensitivity of two HNSCC cell lines, UT-SCC-14 and UT-SCC-45, was assessed using a crystal violet assay and xenografts in nude mice, respectively. The expression of EGFR, phosphorylated EGFR (pEGFR), phosphorylated Src (pSrc), and Ki-67 was investigated by immunohistochemistry. To verify these results, the in vitro expression of EGFR and pEGFR was analyzed with ELISA in a panel of 10 HNSCC cell lines.
  
  
  RESULTS
  A close correlation was found between in vitro and in vivo cetuximab sensitivity data in the two investigated HNSCC cell lines. In treatment sensitive UT-SCC-14 xenografts, there was a decrease in EGFR, pEGFR, and pSrc upon cetuximab treatment. Interestingly, in insensitive UT-SCC-45 xenografts, an increased expression of these three proteins was found. The change in EGFR and pEGFR expression in vivo was confirmed in cetuximab-sensitive and cetuximab-insensitive HNSCC cell lines using ELISA.
  
  
  CONCLUSIONS
  High sensitivity to cetuximab was strongly associated with a treatment-induced reduction in pEGFR both in vivo and in vitro in a panel of HNSCC cell lines, suggesting that EGFR and pEGFR dynamics could be used as a predictive biomarker for cetuximab treatment response.
authors.affiliation: Department of ENT - Head and Neck Surgery, County Council of Östergötland, Linköping, Sweden.
authors.forename: Adam
authors.initials: A
authors.lastname: Jedlinski
authors.affiliation: Department of Clinical Pathology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Stina
authors.initials: S
authors.lastname: Garvin
authors.affiliation: Division of Oto-Rhino-Laryngology and Head and Neck Surgery, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Ann-Charlotte
authors.initials: AC
authors.lastname: Johansson
authors.affiliation: Department of Immunology, Genetics and Pathology and Science for Life Laboratory, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Per-Henrik
authors.initials: PH
authors.lastname: Edqvist
authors.affiliation: Department of Immunology, Genetics and Pathology and Science for Life Laboratory, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Ponten
authors.affiliation: Department of ENT - Head and Neck Surgery, County Council of Östergötland, Linköping, Sweden.|Division of Oto-Rhino-Laryngology and Head and Neck Surgery, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Roberg
mesh_terms: D000818:Animals; D000074322:Antineoplastic Agents, Immunological / Q000494:pharmacology* / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D000068818:Cetuximab / Q000494:pharmacology* / Q000627:therapeutic use*; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000096:biosynthesis / Q000187:drug effects*; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D064593:Heterografts; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D015688:Oncogene Protein pp60(v-src) / Q000096:biosynthesis / Q000187:drug effects*; D010766:Phosphorylation; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D000074322:Antineoplastic Agents, Immunological; C541485:EGFR protein, mouse; D066246:ErbB Receptors; D015688:Oncogene Protein pp60(v-src); D000068818:Cetuximab
keywords: and xenografts; cetuximab; epidermal growth factor receptor; head and neck squamous cell carcinoma; phosphorylated epidermal growth factor receptor