Dataset Information

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.

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-1? 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-1? 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.

SUBMITTER: Wozny AS

PROVIDER: S-EPMC6521340 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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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.

Wozny Anne-Sophie AS Vares Guillaume G Alphonse Gersende G Lauret Alexandra A Monini Caterina C Magné Nicolas N Cuerq Charlotte C Fujimori Akira A Monboisse Jean-Claude JC Beuve Michael M Nakajima Tetsuo T Rodriguez-Lafrasse Claire C

Cancers 20190403 4

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 ...[more]

PMID: 30987217

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Project description:Background and Purpose: Radiotherapy is an essential tool for cancer treatment. In order to spare normal tissues and to reduce the risk of normal tissue complications, particle therapy is a method of choice. Although a large part of healthy tissues can be spared due to improved depth dose characteristics, little is known about the biological and molecular mechanisms altered after particle irradiation in healthy tissues. Elucidation of these effects is also required in the context of long term space flights, as particle radiation is the main contributor to the radiation effects observed in space. Endothelial cells (EC), forming the inner layer of all vascular structures, are especially sensitive to irradiation and, if damaged, contribute to radiation-induced cardiovascular disease. Materials and Methods: Transcriptomics, proteomics and cytokine analyses were used to compare the response of ECs irradiated or not with a single 2 Gy dose of X-rays or Fe ions measured one and 7 days post-irradiation. To support the observed inflammatory effects, monocyte adhesion on ECs was also assessed. Results: Experimental data indicate time- and radiation quality-dependent changes of the EC response to irradiation. The irradiation impact was more pronounced and longer lasting for Fe ions than for X-rays. Both radiation qualities decreased the expression of genes involved in cell-cell adhesion and enhanced the expression of proteins involved in caveolar mediated endocytosis signaling. Endothelial inflammation and adhesiveness were increased with X-rays, but decreased after Fe ion exposure. Conclusions: Fe ions induce pro-atherosclerotic processes in ECs that are different in nature and kinetics than those induced by X-rays, highlighting radiation quality-dependent differences which can be linked to the induction and progression of cardiovascular diseases (CVD). Our findings give a better understanding of the underlying processes triggered by particle irradiation in ECs, a crucial aspect for the development of protective measures for cancer patients undergoing particle therapy and for astronauts in space.

Project description:The present study explored the motivation of rural-urban migrants who moved from the Himalaya foothills of Uttarakhand to its capital city, Dehradun. A survey of 100 migrant families reported their socio-economic profile before and after migration, personal and general reasons for migration, problems in the village and in the city, and perception of push- and pull factors. A remote sensing-based analysis of land cover and forest changes was conducted for two villages of the migrants' origin, aiming to link the reasons for migration to land cover changes. This was contextualised by reported large scale changes in forest cover. Major reasons for migration mentioned in this study were education, employment opportunities with the associated income, and facilities. These were perceived as both, push and pull factors, whereas environmental factors ranked very low. Declining environment or agriculture were never mentioned spontaneously as personal reason, and only occasionally as a presumed general reason for migration, but were frequently confirmed as a major problem in the village. Thus, although such problems existed, they seemed not a major driver of rural-urban migration. For most of the respondents their migration resulted in a profound change of livelihoods and significantly improved their socio-economic situation. Land and forest cover around the chosen villages fluctuated by up to 15% with a trend to increasing forest cover in recent years. At the district and state scales, forest cover was rather stable. These results question the narrative of deforestation and environmental degradation in the Himalayas as major push-factors for rural-urban migration in Uttarakhand. Even if environmental constraints were felt, it was rather the differences in socio-economic opportunities (education, employment, facilities) that drove people to migrate to the city. Regarding the push-pull paradigm, we conclude that scenarios of external conditions under which people migrate cannot be evaluated without taking the migrants' attitudes and choices into account.

Dataset Information

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.

Publications

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.

Similar Datasets

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