title: The kallikrein-kinin-system in head and neck squamous cell carcinoma (HNSCC) and its role in tumour survival, invasion, migration and response to radiotherapy.
abstract: BACKGROUND
  In this study, we investigated the role of the kallikrein-kinin-system in head and neck squamous cell carcinoma (HNSCC) and its implication on tumour survival, invasion, migration and response to radiotherapy.
  
  
  METHODS
  The expression of BKB2R was studied in a series of 180 tumour samples to determine the functional significance of BKB2R in HNSCC. Additionally, four different HNSCC cell lines were treated with an irradiation dose of 8Gy following bradykinin receptor stimulation or blockage. Tumour cell survival was tested using a colony formation assay. The invasive potential of tumour cells was assessed using Matrigel invasion chambers, the cells' ability to migrate was determined with a wound-healing assay. To examine the biochemical activation of BKB2R, the epidermal growth factor receptor (EGFR) and its downstream pathways, western blot analyses were conducted.
  
  
  RESULTS
  Immunohistochemistry revealed an over-expression of BKB2R in HNSCC tumour cells in comparison to normal peritumoural tissue. Blocking the BKB2R at irradiated tumour cells led to a reduced response to radiotherapy of tumour cells and led to an activation of the EGFR and its downstream pathways, known mediators of tumour cell survival, migration and invasion. Bradykinin stimulation also resulted in a better tumour cell survival, but these effects were achieved via an EGFR-independent signalling.
  
  
  CONCLUSIONS
  Our results demonstrate that the kallikrein-kinin-system is involved in survival, invasion and migration of HNSCC cells.
authors: Department of Otolaryngology Head and Neck Surgery, Technical University of Munich, Ismaninger Straße 22, 81675 München, Germany.
authors: Carolin
authors: C
authors: Beck
authors: Guido
authors: G
authors: Piontek
authors: Anna
authors: A
authors: Haug
authors: Murat
authors: M
authors: Bas
authors: Andreas
authors: A
authors: Knopf
authors: Thomas
authors: T
authors: Stark
authors: Martin
authors: M
authors: Mißlbeck
authors: Martina
authors: M
authors: Rudelius
authors: Rudolf
authors: R
authors: Reiter
authors: Markus
authors: M
authors: Brandstetter
authors: Anja
authors: A
authors: Pickhard
mesh_terms: D000328:Adult; D000368:Aged; D015153:Blotting, Western; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D065094:Bradykinin B2 Receptor Antagonists; D045744:Cell Line, Tumor; D004815:Epidermal Growth Factor / Q000378:metabolism; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D007150:Immunohistochemistry; D016234:Kallikrein-Kinin System; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D015398:Signal Transduction
chemical_list: D065094:Bradykinin B2 Receptor Antagonists; D004815:Epidermal Growth Factor; C065679:icatibant; D001920:Bradykinin