Oncotarget

Research Papers:

This article has been corrected. Correction in: Oncotarget. 2019; 10:5889-5889.

Epithelial-mesenchymal crosstalk induces radioresistance in HNSCC cells

Teresa Bernadette Steinbichler _, Abdelmoez Alshaimaa, Metzler Veronika Maria, Dejaco Daniel, Riechelmann Herbert, Dudas Jozsef and Skvortsova Ira-Ida

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Oncotarget. 2018; 9:3641-3652. https://doi.org/10.18632/oncotarget.23248

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Abstract

Teresa Bernadette Steinbichler1, Abdelmoez Alshaimaa2, Metzler Veronika Maria1, Dejaco Daniel1, Riechelmann Herbert1, Dudas Jozsef1 and Skvortsova Ira-Ida2

1Department of Otorhinolaryngology, Medical University of Innsbruck, Innsbruck, Austria

2Department of Therapeutic Radiology and Oncology, Medical University of Innsbruck, Innsbruck, Austria

Correspondence to:

Teresa Bernadette Steinbichler, email: [email protected]

Keywords: epithelial to mesenchymal transition; chemoresistance; clonogenic assays; ERCC1; survivin

Received: April 25, 2017     Accepted: December 04, 2017     Published: December 14, 2017

ABSTRACT

Objective: Epithelial-mesenchymal crosstalk (EMC) contributes to tumor progression, chemoresistance and acquisition of a mesenchymal phenotype (EMT) of cancer cells. This study aims to investigate the effects of EMC on radioresistance in head and neck squamous cell carcinoma (HNSCC) cells.

Methods: In tumor cell lines, the response of HNSCC cells, stimulated with EMC conditioned medium (CM), to irradiation was evaluated with viability and clonogenic assays. Dose modifying factors (DMF) were calculated from the results of clonogenic assays. Potential pathways involved in radioresistance were analyzed with quantitative Real-Time PCR and western blot.

Results: CM significantly reduced the doubling time of SCC-25 cells (from 32.8 hours to 16.8 hours, p=0.0001) and Detroit 562 cells (from 88.5 hours to 29.6 hours, p=0.014). Further it increased clonogenic survival after irradiation. The DMF of CM was 2.04 ± 0.43 (mean ± standard deviation) for SCC-25 cells (p=0.015) and 2.14 ± 0.34 for Detroit 562 cells (p=0.008). Treatment with CM more than tripled the ERCC1 and survivin gene expression in SCC-25 cells.

Conclusion: EMC induced pathways involved in cell survival and DNA repair and led to increased radioresistance in HNSCC cells.


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