CC BY-NC-ND 4.0 · Laryngorhinootologie 2018; 97(S 02): S137-S138
DOI: 10.1055/s-0038-1640187
Abstracts
Onkologie: Oncology

Characterization of phenotype changes after long-term inhibition of EGFR in OSCC and analysis by MALDI-MSI

C Umbreit
1   Klinik für HNO-Heilkunde, Universitätsklinikum Jena, Jena, Deutschland
,
D Tuch
2   Institut für Pathologie, Universitätsklinikum Jena, Jena
,
F Hoffmann
3   Institut für Physikalische Chemie, Friedrich Schiller Universität Jena; linik fü, Jena
,
C Gräfe
4   Klinik für Hämatologie und Onkologie, Universitätsklinikum Jena, Jena
,
JH Clement
4   Klinik für Hämatologie und Onkologie, Universitätsklinikum Jena, Jena
,
M Franz
5   Klinik für Innere Medizin I, Universitätsklinikum Jena, Jena
,
F von Eggeling
6   nstitut für Physikalische Chemie, Friedrich Schiller Universität Jena;linik für, Jena
,
A Berndt
2   Institut für Pathologie, Universitätsklinikum Jena, Jena
,
O Guntinas-Lichius
7   Klinik für HNO-Heilkunde, Universitätsklinikum Jena, Jena
› Author Affiliations
C. Umbreit was supported by a grant of the Interdisciplinary Center for Clinical Research (IZKF).
› Further Information
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    Introduction:

    The epithelial mesenchymal transition (EMT) and cancer stem cell (CSC) development promote therapy resistance in oral squamous cell carcinoma (OSCC), but the mechanisms behind are not fully understood. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) enables a label-free detection of associated molecules within cancer tissue with a possible predictive value.

    Methods:

    UPCI-SCC-026 cells were cultivated under Gefitinib supplementation (5µM) for more than 12 months (SCC026Gef). To detect differences in phenotype, Gefitinib sensitivity, and behavior, cell invasion/migration assays, time-dependent cell response profiles assay (TCRPs), flow cytometry (FCM) and MALDI MSI were performed. Protein-/RNA expression of EMT/CSC markers were detected by immunofluorescence and RT2 Profiler PCR Arrays.

    Results:

    SCC026Gef cells show a spindle shaped scattered growth, increased migration/invasion, and reduced proliferation. The data of FCM and TCRPs indicate a decreased sensitivity to Gefitinib in SCC026Gef. Protein and mRNA expression analyses show an EGFR upregulation, a minimal E-cadherin down-regulation, increased expression of collagen 3α1, fibronectin, and CSC markers (AXL, DLL1, FLOT2, KIT, KIT ligand). A protocol for processing cultured cells for MALDI-MSI analysis was established. Discriminating imaging patterns of SCC026Gef can be detected.

    Conclusions:

    We provide an in vitro model of therapy-induced selection of resistant cell clones in OSCC with a development of a partial EMT/CSC phenotype by long-term EGFR inhibitor treatment. Treatment-induced phenotype changes can be revealed by MALDI-MSI. The predictive value of different imaging patterns of MALDI-MSI has to be validated in further studies.


    #

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

    Priv.-Doz. Dr. med. Claudia Umbreit
    Klinik für HNO-Heilkunde, Universitätsklinikum Jena,
    Am Klinikum 1, 07743,
    Jena,
    Deutschland   

    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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