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Cancers 2019, 11(4), 468; https://doi.org/10.3390/cancers11040468

ROS Production and Distribution: A New Paradigm to Explain the Differential Effects of X-ray and Carbon Ion Irradiation on Cancer Stem Cell Migration and Invasion

1
Laboratoire de Radiobiologie Cellulaire et Moléculaire, Faculté de Médecine Lyon-Sud, Univ Lyon, Université Lyon 1, UMR CNRS5822/IN2P3, IPNL, PRISME, 69921 Oullins CEDEX, France
2
Centre Hospitalier Lyon-Sud, Service de Biochimie et Biologie Moléculaire, Hospices Civils de Lyon, 69495 Pierre-Bénite, France
3
Advanced Medical Instrumentation Unit, Okinawa Institute of Science and Technology Graduate University, Okinawa 904-0495, Japan
4
Department of Radiation Effects Research, National Institute of Radiological Sciences, National Institute for Quantum and Radiological Science and Technology, Inage-ku, Chiba 263-8555, Japan
5
Univ Lyon, Université Lyon 1, UMR CNRS5822 /IN2P3, IPNL, PRISME, PHABIO, 69322 Villeurbanne, France
6
Département de Radiothérapie, Institut de Cancérologie de la Loire Lucien Neuwirth, 42270 St Priest en Jarez, France
7
Department of Basic Medical Sciences for Radiation Damages, National Institute of Radiological Sciences, Inage-ku, 263-8555 Chiba, Japan
8
Université de Reims Champagne-Ardenne, CNRS UMR 7369, CHU de Reims, 51100 Reims, France
*
Author to whom correspondence should be addressed.
Received: 12 February 2019 / Revised: 26 March 2019 / Accepted: 1 April 2019 / Published: 3 April 2019
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Abstract

Although conventional radiotherapy promotes the migration/invasion of cancer stem cells (CSCs) under normoxia, carbon ion (C-ion) irradiation actually decreases these processes. Unraveling the mechanisms of this discrepancy, particularly under the hypoxic conditions that pertain in niches where CSCs are preferentially localized, would provide a better understanding of the origins of metastases. Invasion/migration, proteins involved in epithelial-to-mesenchymal transition (EMT), and expression of MMP-2 and HIF-1α were quantified in the CSC subpopulations of two head-and-neck squamous cell carcinoma (HNSCC) cell lines irradiated with X-rays or C-ions. X-rays triggered HNSCC-CSC migration/invasion under normoxia, however this effect was significantly attenuated under hypoxia. C-ions induced fewer of these processes in both oxygenation conditions. The differential response to C-ions was associated with a lack of HIF-1α stabilization, MMP-2 expression, or activation of kinases of the main EMT signaling pathways. Furthermore, we demonstrated a major role of reactive oxygen species (ROS) in the triggering of invasion/migration in response to X-rays. Monte-Carlo simulations demonstrated that HO radicals are quantitatively higher after C-ions than after X-rays, however they are very differently distributed within cells. We postulate that the uniform distribution of ROS after X-rays induces the mechanisms leading to invasion/migration, which ROS concentrated in C-ion tracks are unable to trigger. View Full-Text
Keywords: X-ray irradiation; carbon ion irradiation; reactive oxygen species; cancer stem cells; hypoxia; metastases; invasion/migration X-ray irradiation; carbon ion irradiation; reactive oxygen species; cancer stem cells; hypoxia; metastases; invasion/migration
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Wozny, A.-S.; Vares, G.; Alphonse, G.; Lauret, A.; Monini, C.; Magné, N.; Cuerq, C.; Fujimori, A.; Monboisse, J.-C.; Beuve, M.; Nakajima, T.; Rodriguez-Lafrasse, C. ROS Production and Distribution: A New Paradigm to Explain the Differential Effects of X-ray and Carbon Ion Irradiation on Cancer Stem Cell Migration and Invasion. Cancers 2019, 11, 468.

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