title: Targeting ErbB-1 and ErbB-4 in irradiated head and neck cancer: results of in vitro and in vivo studies.
abstract: BACKGROUND
  ErbB oncogenes have a major role in cancer. The role of ErbB-4 in cancer cell biology and the effect of anti-ErbB-1 and anti-ErbB-4 monoclonal antibodies were evaluated in this study.
  
  
  METHODS
  ErbB-4 expression and binding was evaluated by Western blot, enzyme-linked immunosorbent assay (ELISA), fluorescent microscopy, and flow cytometry. Cell survival was measured by XTT assay. Tumor progression was followed up in nude mice model.
  
  
  RESULTS
  High ErbB-1 levels in head and neck cancer cell lines were determined, whereas ErbB-4 expression varied. Specific antibody binding to the cells was demonstrated. High ErbB-4 expressing squamous cell carcinoma 1 (SCC-1) cells proliferated faster and generated faster growing tumors in mice. Cetuximab and mAb-3 reduced cell survival proportional to ErbB-1 and ErbB-4 expression. Combination of antibodies with irradiation was most effective in reducing cell survival and tumor growth.
  
  
  CONCLUSIONS
  ErbB-4 plays a role in head and neck cancer cell biology. Anti-ErbB-4 targeted therapy can serve as a new strategy against head and neck cancer when combined with established treatments.
authors.affiliation: Tel Aviv Sourasky Medical Center, Oncology Division, Radiotherapy Unit, Tel Aviv, Israel.
authors.forename: Itay
authors.initials: I
authors.lastname: Barnea
authors.forename: Sasha
authors.initials: S
authors.lastname: Haif
authors.forename: Rom
authors.initials: R
authors.lastname: Keshet
authors.forename: Vicky
authors.initials: V
authors.lastname: Karaush
authors.forename: Shahar
authors.initials: S
authors.lastname: Lev-Ari
authors.forename: Avi
authors.initials: A
authors.lastname: Khafif
authors.forename: Alexander
authors.initials: A
authors.lastname: Shtabsky
authors.forename: Yosef
authors.initials: Y
authors.lastname: Yarden
authors.forename: Akiva
authors.initials: A
authors.lastname: Vexler
authors.forename: Rami
authors.initials: R
authors.lastname: Ben Yosef
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000068818:Cetuximab; D004797:Enzyme-Linked Immunosorbent Assay; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D005434:Flow Cytometry; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D066247:Receptor, ErbB-4; D000077195:Squamous Cell Carcinoma of Head and Neck; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C587689:ERBB4 protein, human; D066246:ErbB Receptors; C587690:Erbb4 protein, mouse; D066247:Receptor, ErbB-4; D000068818:Cetuximab