Characterization of phenotype changes after long-term inhibition of EGFR in OSCC and analysis by MALDI-MSI
Year: 2018
Type: conference-paper
Abstract: 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. 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/). Georg Thieme Verlag KG Stuttgart · New York
Source: Laryngo-Rhino-Otologie
Authors: C Umbreit, D Tuch, F Hoffmann, C Gräfe, JH Clement, M Franz, F Eggeling, A Berndt, O Guntinas-Lichius
Institutions: Jena University Hospital, Friedrich Schiller University Jena
Language: English
Topic: Cancer Cells and Metastasis
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W2885011537