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Open Access Highly Accessed Research article

Inhibition of radiation induced migration of human head and neck squamous cell carcinoma cells by blocking of EGF receptor pathways

Anja C Pickhard1*, Johanna Margraf1, Andreas Knopf1, Thomas Stark1, Guido Piontek1, Carolin Beck1, Anne-Laure Boulesteix3, Elias Q Scherer1, Steffi Pigorsch4, Jürgen Schlegel2, Wolfgang Arnold1 and Rudolf Reiter5

Author Affiliations

1 Department of Otolaryngology Head and Neck Surgery, Technical University of Munich, Ismaninger Straße 22, 81675 Munich, Germany

2 Institute of Pathology, Section of Neuropathology, Technical University of Munich, Ismaninger Straße 22, 81675 Munich, Germany

3 Institute for Statistics, Ludwig-Maximilians-University Munich, Ludwigstraße 33, 80539 Munich, Germany

4 Department of Radiotherapy, Technical University of Munich, Ismaninger Straße 22, 81675 Munich, Germany

5 Department of Otolaryngology Head and Neck Surgery, Section of Phoniatrics and Pedaudiology, University of Ulm, Prittwitzstr. 43, 89070 Ulm, Germany

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BMC Cancer 2011, 11:388  doi:10.1186/1471-2407-11-388

Published: 6 September 2011

Abstract

Background

Recently it has been shown that radiation induces migration of glioma cells and facilitates a further spread of tumor cells locally and systemically. The aim of this study was to evaluate whether radiotherapy induces migration in head and neck squamous cell carcinoma (HNSCC). A further aim was to investigate the effects of blocking the epidermal growth factor receptor (EGFR) and its downstream pathways (Raf/MEK/ERK, PI3K/Akt) on tumor cell migration in vitro.

Methods

Migration of tumor cells was assessed via a wound healing assay and proliferation by a MTT colorimeritric assay using 3 HNSCC cell lines (BHY, CAL-27, HN). The cells were treated with increasing doses of irradiation (2 Gy, 5 Gy, 8 Gy) in the presence or absence of EGF, EGFR-antagonist (AG1478) or inhibitors of the downstream pathways PI3K (LY294002), mTOR (rapamycin) and MEK1 (PD98059). Biochemical activation of EGFR and the downstream markers Akt and ERK were examined by Western blot analysis.

Results

In absence of stimulation or inhibition, increasing doses of irradiation induced a dose-dependent enhancement of migrating cells (p < 0.05 for the 3 HNSCC cell lines) and a decrease of cell proliferation (p < 0.05 for the 3 HNSCC cell lines). The inhibition of EGFR or the downstream pathways reduced cell migration significantly (almost all p < 0.05 for the 3 HNSCC cell lines). Stimulation of HNSCC cells with EGF caused a significant increase in migration (p < 0.05 for the 3 HNSCC cell lines). After irradiation alone a pronounced activation of EGFR was observed by Western blot analysis.

Conclusion

Our results demonstrate that the EGFR is involved in radiation induced migration of HNSCC cells. Therefore EGFR or the downstream pathways might be a target for the treatment of HNSCC to improve the efficacy of radiotherapy.