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Evaluation of FGFR3 as a Therapeutic Target in Head and Neck Squamous Cell Carcinoma

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Abstract

Background

Although head and neck squamous cell carcinoma (HNSCC) is the sixth most common tumour entity worldwide, it remains a clinical challenge. Large-scale explorative genomic projects have identified several genes as potential targets for therapy, including fibroblast growth factor receptor 3 (FGFR3).

Aims

The aim of this study was to investigate the biological significance of wild-type and mutated FGFR3 to evaluate its potential as a novel therapeutic target in HNSCC.

Methods

FGFR3 protein expression was analysed in a large HNSCC tissue cohort (n = 536) and FGFR3 mRNA expression from The Cancer Genome Atlas (TCGA; n = 520). Moreover, FGFR3 wild-type and mutant versions were overexpressed in vitro, and both proliferation and migration was assessed with and without BGJ398 (a specific FGFR1-3 inhibitor) treatment.

Results

Although FGFR3 expression for both cohorts decreased during tumour progression, high FGFR3 expression levels were observed in a small subset of patients. In vitro, FGFR3 overexpression led to increased proliferation, whereas migration was not altered. Moreover, FGFR3-overexpressing cells were more sensitive to BGJ398. Cells overexpressing FGFR3 mutant versions showed increased proliferation compared to wild-type FGFR3 under serum-reduced conditions and were largely as sensitive as the wild-type protein to BGJ398.

Conclusions

Taken together, the results of this study demonstrate that although FGFR3 expression decreases during HNSSC progression, it plays an important role in tumour cell proliferation and thus may be a potential target for therapy in selected patients suffering from this dismal tumour entity.

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    Authors and Affiliations

    1. Section of Prostate Cancer Research, University Hospital of Bonn, Bonn, Germany

      Anne von Mässenhausen, Hannah Billig, Angela Queisser, Friederike Göke, Alina Franzen & Johannes Brägelmann

    2. Institute of Pathology, University Hospital of Bonn, Bonn, Germany

      Anne von Mässenhausen, Hannah Billig, Angela Queisser, Glen Kristiansen, Friederike Göke, Alina Franzen & Jutta Kirfel

    3. Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany

      Anne von Mässenhausen, Hannah Billig, Angela Queisser, Glen Kristiansen, Andreas Schröck, Friedrich Bootz, Friederike Göke, Alina Franzen, Jutta Kirfel & Johannes Brägelmann

    4. Pathology of the University Hospital of Luebeck, Luebeck, Germany

      Mario Deng, Wenzel Vogel & Sven Perner

    5. Department of Pathology, Leibniz Research Center Borstel, Borstel, Germany

      Mario Deng, Wenzel Vogel & Sven Perner

    6. Department of Otorhinolaryngology/Head and Neck Surgery, University Hospital of Bonn, Bonn, Germany

      Andreas Schröck & Friedrich Bootz

    7. Department of Craniofacial Biology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA

      Lynn Heasley

    8. Department of Hematology/Oncology, University Hospital of Bonn, Bonn, Germany

      Johannes Brägelmann

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    1. Anne von Mässenhausen
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    Correspondence to Sven Perner.

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    Funding

    This study was supported by a BONFOR grant (2014-6-11) of the Medical Faculty of the University of Bonn to JB.

    Conflict of interest

    AvM, MD, HB, AQ, WV, GK, AS, FB, FG, AF, LH, JK, JB and SP declare that they have no financial or personalconflict of interest.

    Ethical Approval

    This retrospective study involving human participants was performed in accordance with the ethical standards of the institutional and national research committees and the 1964 Declaration of Helsinki, and was approved by the institutional ethics review board of the University of Bonn (#148/11).

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    Johannes Brägelmann and Sven Perner contributed equally to this work.

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    von Mässenhausen, A., Deng, M., Billig, H. et al. Evaluation of FGFR3 as a Therapeutic Target in Head and Neck Squamous Cell Carcinoma. Targ Oncol 11, 631–642 (2016). https://doi.org/10.1007/s11523-016-0431-z

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