The kallikrein-kinin-system in head and neck squamous cell carcinoma (HNSCC) and its role in tumour survival, invasion, migration and response to radiotherapy

Carolin Beck, Guido Piontek, Anna Haug, Murat Bas, Andreas Knopf, Thomas Stark, Martin Mißlbeck, Martina Rudelius, Rudolf Reiter, Markus Brandstetter, Anja Pickhard

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

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 8 Gy 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.

Original languageEnglish
Pages (from-to)1208-1219
Number of pages12
JournalOral Oncology
Volume48
Issue number12
DOIs
StatePublished - Dec 2012
Externally publishedYes

Keywords

  • Bradykinin
  • EGFR
  • HNSCC
  • Kallikrein-kinin-system

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