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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.00825

Exploring radiation response in two head & neck squamous cell carcinoma cell lines through metabolic profiling

Eva Lindell Jonsson1,  Ida Erngren2, Mikael Engskog2, Jakob Haglöf2, Torbjörn Arvidsson2, 3,  Mikael Hedeland2, Curt Pettersson2,  Göran Laurell1 and  Marika Nestor4*
  • 1Department of Surgical Sciences, Uppsala University, Sweden
  • 2Department of Medicinal Chemistry, Uppsala University, Sweden
  • 3Medical Products Agency, Sweden
  • 4Department of Immunology, Genetics and Pathology, Uppsala University, Sweden

Head and neck squamous cell carcinoma is the sixth most common form of cancer worldwide. Radiotherapy, with or without surgery, represents the major approach to curative treatment. However, not all tumours are equally sensitive to irradiation. It is therefore of interest to apply newer system biology approaches (e.g metabolic profiling) in squamous cancer cells with different radiosensitivities in order to provide new insights on the mechanisms of radiation response. In this study, two cultured head and neck squamous cell carcinoma cell lines from the same donor, UM-SCC-74A and UM-SCC-74B, were first genotyped using STR, and assessed for radiation response by the means of clonogenic survival and growth inhibition assays. Thereafter, cells were cultured, irradiated and collected for subsequent metabolic profiling analyses using liquid chromatography-mass spectrometry (LC-MS). STR verified the similarity of UM-SCC-74A and UM-SCC-74B cells, and three independent assays proved UM-SCC-74B to be clearly more radioresistant than UM-SCC-74A. The LC-MS metabolic profiling demonstrated significant differences in the intracellular metabolome of the two cell lines before irradiation, as well as significant alterations after irradiation. The most important differences between the two cell lines before irradiation were connected to nicotinic acid and nicotinamide metabolism and purine metabolism. In the more radiosensitive UM-SCC-74A cells, the most significant alterations after irradiation were linked to tryptophan metabolism. In the more radioresistant UM-SCC-74B cells, the major alterations after irradiation were connected to nicotinic acid and nicotinamide metabolism, purine metabolism, the methionine cycle as well as the serine and glycine metabolism. The data suggest that the more radioresistant cell line UM-SCC-74B altered the metabolism to control redox-status, manage DNA-repair and change DNA methylation after irradiation. This provides new insights on the mechanisms of radiation response, which may aid future identification of biomarkers associated with radioresistance of cancer cells.

Keywords: radiation response, metabolic profiling, biomarkers, radioresistance mechanisms, radiosensitivity, head and neck cancer, Mass Spectrometry

Received: 17 Apr 2019; Accepted: 12 Aug 2019.

Copyright: © 2019 Lindell Jonsson, Erngren, Engskog, Haglöf, Arvidsson, Hedeland, Pettersson, Laurell and Nestor. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Marika Nestor, Uppsala University, Department of Immunology, Genetics and Pathology, Uppsala, Sweden, marika.nestor@igp.uu.se