Spatial ROS distribution to explains the differences in the invasion/migration processes of cancer stem cells in response to photons and carbon ions - Archive ouverte HAL Accéder directement au contenu
Communication Dans Un Congrès Année : 2018

Spatial ROS distribution to explains the differences in the invasion/migration processes of cancer stem cells in response to photons and carbon ions

Résumé

The epithelio-mesenchymal transition (EMT) is the mechanism that allows cells to escape from the tumor to form metastases. While conventional radiotherapy promotes the invasion/migration of cancer stem cells (CSCs), carbon ion irradiation decrease these processes. Moreover, CSCs are localized in hypoxic tumor niches where hypoxia amplifies the biological effects associated with radioresistance. Thus, understanding the differential mechanisms involved in the response to photon and carbon ion irradiation, particularly in hypoxic conditions, would provide a better understanding of the tumor escape process. Motility, invasion/migration processes, and EMT signaling pathways were studied in response to photon and carbon ion irradiations for two HNSCC cell lines and their subpopulation of CSCs in normoxic and hypoxic conditions. After confirming, in normoxic conditions, the invasion/migration increase in response to photons and the decrease after irradiation with carbon ions, we have shown that under hypoxia, the two types of irradiation lead to a decrease in the processes. In order to understand this differential response to radiations, the phosphorylation profiles of the Akt/mTor, STAT3 and ERK/p38/MSK pathways involved in the EMT were established. In response to photons, the activation of the three kinase cascades is important, whereas it is weaker in hypoxia, and not at all in response to carbon ion irradiation regardless of the oxygen tension. Our results show a phosphorylation profile of the three main EMT pathways, depending on the type of irradiation and the oxygen tension. ROS production is essential to activate the EMT pathways. We propose a new paradigm where the spatial ROS distribution contribute to the activation or not of the signaling pathways. The ROS production, uniformly distributed in the cell in response to photons allows the activation of the pathways unlike carbon ions where the ROS are only located in the carbon ion tracks and not sufficient to activate the EMT pathways. Supported by LabEx PRIMES (ANR11LABX0063), France Hadron (ANR11INBS0007), Cancéropôle Rhone Alpes Auvergne.
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Dates et versions

hal-02063655 , version 1 (11-03-2019)

Identifiants

  • HAL Id : hal-02063655 , version 1

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Anne-Sophie Wozny, Gersende Alphonse, Guillaume Vares, Caterina Monini, Jean-Baptiste Guy, et al.. Spatial ROS distribution to explains the differences in the invasion/migration processes of cancer stem cells in response to photons and carbon ions. 64th Annual Meeting of the Radiation Research Society, Sep 2018, Chicago, United States. ⟨hal-02063655⟩
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