@article{oai:repo.qst.go.jp:00075822, author = {WOZNY, Anne-Sophie and Vares, Guillaume and Gersende, ALPHONSE and Lauret, Alexandra and Monini, Caterina and Magne, Nicolas and Cuerq, Charlotte and 藤森, 亮 and Jean-Claude, Monboisse and Beuve, Michael and 中島, 徹夫 and RODRIGUEZ-LAFRASSE, Claire and Wozny, Annesophie and Vares, Guillaume and Alphonse, Gersende and Fujimori, Akira and Nakajima, Tetsuo and Rodriguezlafrasse, Claire}, issue = {468}, journal = {Cancers}, month = {Apr}, note = {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.}, title = {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}, volume = {11}, year = {2019} }