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

    Publikationsverlauf

    Publikationsdatum:
    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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