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Epidermal growth factor-induced modulation of cytokeratin expression levels influences the morphological phenotype of head and neck squamous cell carcinoma cells

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Abstract

The migratory ability of tumor cells requires cytoskeletal rearrangement processes. Epidermal growth factor receptor (EGFR)-signaling tightly correlates with tumor progression in head and neck squamous cell carcinomas (HNSCCs), and has previously been implicated in the regulation of cytokeratin (CK) expression. In this study, HNSCC cell lines were treated with EGF, and CK expression levels were monitored by Western blot analysis. Changes in cellular morphology were documented by fluorescence- and atomic force microscopy. Some of the cell lines demonstrated an EGF-dependent modulation of CK expression levels. Interestingly, regression of some CK subtypes or initial up-regulation followed by downregulation at higher EGF-levels could also be observed in the tested cell lines. Overall, the influence of EGF on CK expression levels appeared variable and cell-type-dependent. Real-time cellular analysis of EGF-treated and -untreated HNSCC cell lines demonstrated a rise over time in cellular impedance. In three of the EGF-treated HNSCC cell lines, this rise was markedly higher than in untreated controls, whereas in one of the cell lines the gain of cellular impedance was paradoxically reduced after EGF treatment, which was found to correlate with changes in cellular morphology rather than with relevant changes in cellular viability or proliferation. After treating HNSCC cells with EGF, CK filaments frequently appeared diffusely distributed throughout the cytoplasm, and in some cases were found in a perinuclear localization, the latter being reminiscent to observations by other groups. In summary, the data points to a possible role of EGFR in modulating HNSCC cell morphology.

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Acknowledgments

Technical assistance of Ms. Roswitha Peldszus and Ms. Grazyna Sadowski (both Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Giessen and Marburg, Campus Marburg, Marburg, Germany) and Ms. Viktoria Morokina (Institute of Pathology, University Hospital Giessen and Marburg GmbH, Campus Marburg, Marburg, Germany) was greatly appreciated.

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Authors and Affiliations

  1. Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Giessen and Marburg, Campus Marburg, 3. BA, +3/08070, Baldingerstrasse, 35033, Marburg, Germany

    Galina Makarova, Chengzhong Cai, Fiona Rodepeter, Andreas Sesterhenn, Afshin Teymoortash, Jochen A. Werner & Robert Mandic

  2. Department of Molecular Neuroscience, Institute of Anatomy and Cell Biology, Philipps University, Marburg, Germany

    Michael Bette

  3. Institute of Pathology, Philipps University of Marburg, Marburg, Germany

    Ansgar Schmidt & Roland Moll

  4. Department of Cell Biology and Cell Pathology, Philipps University, Marburg, Germany

    Ralf Jacob

  5. Department of Pharmaceutical Technology and Biopharmacy, Philipps University, Marburg, Germany

    Thomas Betz, Johannes Sitterberg & Udo Bakowsky

  6. Department of Oral and Maxillofacial Surgery, University Hospital Giessen and Marburg, Campus Marburg, Medical Faculty of Philipps University, Marburg, Germany

    Andreas Neff

  7. Institute for Surgical Research, Philipps University, Marburg, Germany

    Matthias Ocker

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  1. Galina Makarova
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  3. Ansgar Schmidt
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  5. Chengzhong Cai
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  16. Robert Mandic
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Correspondence to Robert Mandic.

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This study was partly funded by the “Alfred und Ursula Kulemann Stiftung”.

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Makarova, G., Bette, M., Schmidt, A. et al. Epidermal growth factor-induced modulation of cytokeratin expression levels influences the morphological phenotype of head and neck squamous cell carcinoma cells. Cell Tissue Res 351, 59–72 (2013). https://doi.org/10.1007/s00441-012-1500-y

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  • DOI: https://doi.org/10.1007/s00441-012-1500-y

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