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Author
M.C. de Jong
J.J. ten Hoeve
R. Grénman
L.F. Wessels
R. Kerkhoven
H. te Riele
M.W.M. van den Brekel
M. Verheij
A.C. Begg
Year
2015
Title
Pretreatment microRNA Expression Impacting on Epithelial-to-Mesenchymal Transition Predicts Intrinsic Radiosensitivity in Head and Neck Cancer Cell Lines and Patients
Journal
Clinical Cancer Research
Volume | Issue number
21 | 4
Pages (from-to)
5630-5638
Document type
Article
Faculty
Faculty of Dentistry (ACTA)
Faculty of Humanities (FGw)
Faculty of Medicine (AMC-UvA)
Institute
Amsterdam Center for Language and Communication (ACLC)
Abstract
Purpose: Predominant causes of head and neck cancer recurrence after radiotherapy are rapid repopulation, hypoxia, fraction of cancer stem cells, and intrinsic radioresistance. Currently, intrinsic radioresistance can only be assessed by ex vivo colony assays. Besides being time-consuming, colony assays do not identify causes of intrinsic resistance. We aimed to identify a biomarker for intrinsic radioresistance to be used before start of treatment and to reveal biologic processes that could be targeted to overcome intrinsic resistance.

Experimental Design: We analyzed both microRNA and mRNA expression in a large panel of head and neck squamous cell carcinoma (HNSCC) cell lines. Expression was measured on both irradiated and unirradiated samples. Results were validated using modified cell lines and a series of patients with laryngeal cancer.

Results: miRs, mRNAs, and gene sets that correlated with resistance could be identified from expression data of unirradiated cells. The presence of epithelial-to-mesenchymal transition (EMT) and low expression of miRs involved in the inhibition of EMT were important radioresistance determinants. This finding was validated in two independent cell line pairs, in which the induction of EMT reduced radiosensitivity. Moreover, low expression of the most important miR (miR-203) was shown to correlate with local disease recurrence after radiotherapy in a series of patients with laryngeal cancer.

Conclusions: These findings indicate that EMT and low expression of EMT-inhibiting miRs, especially miR-203, measured in pretreatment material, causes intrinsic radioresistance of HNSCC, which could enable identification and treatment modification of radioresistant tumors. Clin Cancer Res; 21(24); 5630-8. ©2015 AACR.
URL
go to publisher's site
Language
English
Permalink
http://hdl.handle.net/11245/1.502847

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