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Expression of Snail is associated with myofibroblast phenotype development in oral squamous cell carcinoma

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Abstract

Snail is a regulator of epithelial–mesenchymal transition (EMT) and considered crucial to carcinoma metastasis, myofibroblast transdifferentiation, and fibroblast activation. To investigate the role of Snail in oral squamous cell carcinoma (OSCC), its immunohistochemical expression was analysed in 129 OSCC samples and correlated to nodal metastasis, histological grade, E-cadherin, and alpha smooth-muscle-actin (αSMA). The results were compared to findings in 23 basal cell carcinomas (BCC). Additionally, the influence of TGFβ1 and EGF on Snail, E-cadherin, vimentin, and αSMA expression was analysed in two OSCC cell lines. As a result, Snail-positive cells were mainly found in the stroma of the OSCC invasive front without statistically significant correlation to histological grade or nodal metastasis. Snail was co-localised to αSMA but not to E-cadherin or cytokeratin and showed a significant correlation to the loss of membranous E-cadherin. All BCCs were Snail negative. In OSCC culture, the growth-factor-mediated EMT-like phenomenon was accompanied by αSMA down-regulation. In summary, Snail expression in OSCC is a stromal phenomenon associated with the myofibroblast phenotype and not related to growth-factor-mediated transdifferentiation of the carcinoma cells themselves. Consequently, Snail immunohistochemistry cannot contribute to the prediction of the metastatic potential. Furthermore, stromal Snail expression is suggested to be the result of mutual paracrine interaction of fibro-/myofibroblasts and dedifferentiated carcinoma cells leading to the generation of a special type of carcinoma-associated fibroblasts.

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Acknowledgements

The authors would like to thank Susanne Bergmann, Christiane Geier, Angela Gröbner, and Katrin Schlehahn for excellent technical assistance. The study was supported by the Thuringian Ministry of Science, Research and Art (ThMWFK), and IZKF of the University Hospital Jena.

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Authors and Affiliations

  1. Clinic of Internal Medicine I, University Hospital Jena, 07740, Jena, Germany

    Marcus Franz

  2. Institute of Pathology, University Hospital Jena, Ziegelmühlenweg 1, 07740, Jena, Germany

    Claudia Umbreit, Petra Richter, Carolina Codina-Canet & Alexander Berndt

  3. Friedrich-Loeffler-Institute, Institute of Molecular Pathogenesis, 07743, Jena, Germany

    Angela Berndt

  4. Tumour Registrary, University Hospital Jena, 07740, Jena, Germany

    Annelore Altendorf-Hofmann

  5. ENT Department, University Hospital Jena, 07740, Jena, Germany

    Karin Spiegel & Sven Koscielny

  6. Clinic of Maxillofacial Surgery/Plastic Surgery, University Hospital Jena, 07740, Jena, Germany

    Peter Hyckel

  7. Institute of Pathology, HELIOS-Klinikum, 99012, Erfurt, Germany

    Hartwig Kosmehl

  8. Institute of Biomedicine/Anatomy, University of Helsinki, 00014, Helsinki, Finland

    Ismo Virtanen

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  1. Marcus Franz
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  2. Karin Spiegel
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  3. Claudia Umbreit
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  5. Carolina Codina-Canet
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  6. Angela Berndt
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  7. Annelore Altendorf-Hofmann
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  8. Sven Koscielny
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  9. Peter Hyckel
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  10. Hartwig Kosmehl
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  12. Alexander Berndt
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Correspondence to Alexander Berndt.

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M. Franz and K. Spiegel have contributed equally to the study.

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Franz, M., Spiegel, K., Umbreit, C. et al. Expression of Snail is associated with myofibroblast phenotype development in oral squamous cell carcinoma. Histochem Cell Biol 131, 651–660 (2009). https://doi.org/10.1007/s00418-009-0559-3

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