Open Access
CC BY-NC-ND 4.0 · Laryngorhinootologie 2018; 97(S 02): S94-S95
DOI: 10.1055/s-0038-1640039
Abstracts
Onkologie: Oncology

Tumor cell plasticity in the pathogenesis and prognosis of head and neck cancer

J Hess
1   Universitätsklinikum Heidelberg, Heidelberg
,
S Homann
1   Universitätsklinikum Heidelberg, Heidelberg
,
N Koerich Laureano
2   DKFZ Heidelberg, Heidelberg
,
B Tawk
1   Universitätsklinikum Heidelberg, Heidelberg
,
M Bieg
2   DKFZ Heidelberg, Heidelberg
,
X Pastor Hostenech
2   DKFZ Heidelberg, Heidelberg
,
K Freier
3   Universitatsklinikum Heidelberg, Heidelberg
,
W Weichert
4   Technische Universität München, München
,
K Zaoui
1   Universitätsklinikum Heidelberg, Heidelberg
,
J Hess
1   Universitätsklinikum Heidelberg, Heidelberg
› Author Affiliations

DKFZ-HIPO (Heidelberg Center for Personalized Oncology), NCT-POP (Precision Oncology Program), iMed Funding Program (Helmholtz Initiative on Personalized Medicine)
› Further Information
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    Introduction:

    Experimental and clinical studies support a model in which a distinct subpopulation of invasive and therapy resistant cancer cells drives treatment failure in head and neck cancer (HNC). Common features of this subpopulation are a high degree of cellular plasticity and acquisition of a phenotype, which is known as epithelial-to-mesenchymal transition. Recently, we unraveled the transcription factor SOX2 as a key regulator of cancer cell plasticity, but the mode of SOX2 regulation remained largely elusive.

    Methods:

    Immunofluorescence staining of cancer cells in 2D and 3D models was done to investigate SOX2 expression on a single cell level. HNC cells were treated with Decitabine (DAC), a potent DNMT inhibitor, to address the impact of DNA methylation on SOX2 expression and cancer cell motility. Integrative multi-scale analysis was performed on global genome, methylome and transcriptome data, which were available for a cohort of 80 HNC patients. Data were confirmed with public available data from the TCGA-HNC cohort.

    Results:

    Heterogeneous SOX2 expression was detected for several HNC cell lines in 2D and 3D models, and loss of SOX2 was a characteristic feature for cells with migratory and invasive properties. DAC treatment restored SOX2 expression accompanied by a decrease in cancer cell migration and invasion, suggesting regulation of heterogeneous SOX2 expression by DNA methylation. In line with this assumption, SOX2 gene promoter methylation was found as a common event in a HNC patient cohort and was confirmed in the TCGA-HNC cohort.

    Conclusion:

    Epigenetic regulation of SOX2 expression by DNA methylation regulates tumor cell plasticity and motility, and treatment with DNMT inhibitors serves as a promising new strategy to prevent tumor cell dissemination.


     

    No conflict of interest has been declared by the author(s).

    Prof. Dr. rer. nat. Jochen Hess
    Universitätsklinikum Heidelberg,
    Im Neuenheimer Feld 400, 69120,
    Heidelberg

    Publication History

    Publication Date:
    18 April 2018 (online)

    © 2018. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

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