title: Enhanced radiosensitivity of head and neck squamous cell carcinoma cells by β1 integrin inhibition.
abstract: OBJECTIVE
  Integrin-mediated adhesion to extracellular matrix (ECM) contributes to the regulation of the cellular radiation response in various tumor entities. To evaluate whether targeting of β1 integrin enhances the radiosensitivity of head and neck SCC cell lines (HNSCC) was assessed using either inhibitory anti-β1 integrin antibodies or specific β1 integrin small interfering RNA (siRNA).
  
  
  METHODS
  The HNSCC cell lines FaDu, UTSCC15 and UTSCC14 were used. Upon β1 integrin inhibition, colony formation, proliferation, DNA double strand breaks, adhesion, and migration as well as protein expression and phosphorylation of integrin downstream targets like Focal Adhesion Kinase and AKT were determined.
  
  
  RESULTS
  We found that siRNA- and antibody-mediated targeting of β1 integrin result in a dose- and cell line-dependent radiosensitization that was accompanied by a decreased cell proliferation and an increased number of radiogenic DNA double strand breaks. Analysis of signal transduction events revealed a dephosphorylation of focal adhesion proteins, prevention of radiation-induced phosphorylation of pro-survival protein kinases and impaired cell adhesion and migration upon blocking of β1 integrins.
  
  
  CONCLUSIONS
  Our data suggest that β1 integrin critically contributes to the cellular radioresistance of HNSCC. Further studies are warranted to evaluate whether targeting β1 integrin emerges as novel approach to improve radiotherapy patients' outcome.
authors: OncoRay-National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Germany.
authors: Iris
authors: I
authors: Eke
authors: Ellen
authors: E
authors: Dickreuter
authors: Nils
authors: N
authors: Cordes
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000532:radiotherapy; D002448:Cell Adhesion / Q000187:drug effects / Q000528:radiation effects*; D045744:Cell Line, Tumor / Q000528:radiation effects*; D002465:Cell Movement / Q000187:drug effects / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D002470:Cell Survival / Q000502:physiology; D005455:Fluorescent Antibody Technique; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D019012:Integrin beta1 / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000528:radiation effects; D034741:RNA, Small Interfering; D011836:Radiation Tolerance / Q000187:drug effects*; D011839:Radiation, Ionizing; D012680:Sensitivity and Specificity; D000077195:Squamous Cell Carcinoma of Head and Neck; D013234:Stem Cells; D014162:Transfection
chemical_list: D000911:Antibodies, Monoclonal; D019012:Integrin beta1; D034741:RNA, Small Interfering