Reference : Preconditioning of the Tumor Vasculature and Tumor Cells by Intermittent Hypoxia: Implic...
Scientific journals : Article
Human health sciences : Oncology
http://hdl.handle.net/2268/73972
Preconditioning of the Tumor Vasculature and Tumor Cells by Intermittent Hypoxia: Implications for Anticancer Therapies
English
[fr] Préconditionnement de la vascularisation des tumeurs et des cellules tumorales par l'hypoxie intermittente: Implications pour les traitements anticancéreux
Martinive, Philippe mailto [Université de Liège - ULg > > Radiothérapie >]
DEFRESNE, Florence [ > > ]
BOUZIN, Caroline [ > > ]
SALIEZ, Julie [ > > ]
LAIR, Florence [ > > ]
GREGOIRE, Vincent [ > > ]
MICHIELS, Carine [ > > ]
DESSY, Chantal [ > > ]
FERON, Olivier [ > > ]
15-Dec-2006
Cancer Research
American Association for Cancer Research, Inc. (AACR)
66
24
11736-44
Yes (verified by ORBi)
International
0008-5472
1538-7445
Baltimore
MD
[fr] microcirculation tumorale ; # # tumor hypoxia hypoxie tumorale ; microenvironnement tumoral ; des cellules endothéliales ; angiogenèse ; HIF-1α ; résistance aux radiations
[en] Tumor microcirculation ; tumor hypoxia ; tumor microenvironment ; endothelial cell ; angiogenesis ; radiation resistance ; HIF-1α
[fr] L'hypoxie est une caractéristique commune des tumeurs associées à une résistance accrue des cellules tumorales aux traitements. In addition to O 2 diffusion–limited hypoxia, another form of tumor hypoxia characterized by fluctuating changes in p O 2 within the disorganized tumor vascular network is described. En plus de O 2-limité hypoxie de diffusion, une autre forme d'hypoxie tumorale caractérisée par la fluctuation des changements dans p O 2 dans la tumeur désorganisé réseau vasculaire est décrite. Here, we postulated that this form of intermittent hypoxia promotes endothelial cell survival, thereby extending the concept of hypoxia-driven resistance to the tumor vasculature. Ici, nous avons postulé que cette forme de l'hypoxie intermittente favorise la survie des cellules endothéliales, ce qui étend la notion de résistance à l'hypoxie axée sur la vascularisation des tumeurs. We found that endothelial cell exposure to cycles of hypoxia reoxygenation not only rendered them resistant to proapoptotic stresses, including serum deprivation and radiotherapy, but also increased their capacity to migrate and organize in tubes. Nous avons trouvé que l'exposition des cellules endothéliales à des cycles de réoxygénation hypoxie non seulement rendus plus résistantes aux contraintes pro-apoptotiques, y compris la privation de sérum et de la radiothérapie, mais aussi accru leur capacité à migrer et à organiser dans les tubes. By contrast, prolonged hypoxia failed to exert protective effects and even seemed deleterious when combined with radiotherapy. En revanche, l'hypoxie prolongée n'a pas d'exercer des effets protecteurs et semblait même nocive en combinaison avec la radiothérapie. The use of hypoxia-inducible factor-1α (HIF-1α)–targeting small interfering RNA led us to document that the accumulation of HIF-1α during intermittent hypoxia accounted for the higher resistance of endothelial cells. L'utilisation de hypoxia-inducible factor-1α (HIF-1α)-ciblage des petits ARN interférents nous a conduit au document que l'accumulation de HIF-1α au cours de l'hypoxie intermittente représentaient la plus grande résistance des cellules endothéliales. We also used an in vivo approach to enforce intermittent hypoxia in tumor-bearing mice and found that it was associated with less radiation-induced apoptosis within both the vascular and the tumor cell compartments (versus normoxia or prolonged hypoxia). Nous avons également utilisé une approche in vivo d'appliquer hypoxie intermittente en portant une tumeur des souris et ont constaté qu'elle était associée à une apoptose induite par radiation moins dans les deux compartiments vasculaires et les cellules tumorales (par rapport à la normoxie ou d'hypoxie prolongée). Radioresistance was further ascertained by an increased rate of tumor regrowth in irradiated mice preexposed to intermittent hypoxia and confirmed in vitro using distinctly radiosensitive tumor cell lines. Radiorésistance a également été constatée par une augmentation du taux de repousse des tumeurs chez des souris irradiées préexposés à une hypoxie intermittente et confirmée in vitro en utilisant distinctement radiosensibles lignées de cellules tumorales. In conclusion, we have documented that intermittent hypoxia may condition endothelial cells and tumor cells in such a way that they are more resistant to apoptosis and more prone to participate in tumor progression. En conclusion, nous avons démontré que l'hypoxie intermittente peut conditionner les cellules endothéliales et les cellules tumorales de telle sorte qu'ils sont plus résistants à l'apoptose et plus enclins à participer à la progression tumorale. Our observations also underscore the potential of drugs targeting HIF-1α to resensitize the tumor vasculature to anticancer treatments. Nos observations soulignent également le potentiel de médicaments ciblant HIF-1α à resensitize la vascularisation des tumeurs aux traitements anticancéreux. (Cancer Res 2006; 66(24): 11736-44) (Cancer Res 2006; 66 (24): de 11736 à 44)
[en] Hypoxia is a common feature in tumors associated with an increased resistance of tumor cells to therapies. In addition to O2 diffusion–limited hypoxia, another form of tumor hypoxia characterized by fluctuating changes in pO2 within the disorganized tumor vascular network is described. Here, we postulated that this form of intermittent hypoxia promotes endothelial cell survival, thereby extending the concept of hypoxia-driven resistance to the tumor vasculature. We found that endothelial cell exposure to cycles of hypoxia reoxygenation not only rendered them resistant to proapoptotic stresses, including serum deprivation and radiotherapy, but also increased their capacity to migrate and organize in tubes. By contrast, prolonged hypoxia failed to exert protective effects and even seemed deleterious when combined with radiotherapy. The use of hypoxia-inducible factor-1α (HIF-1α)–targeting small interfering RNA led us to document that the accumulation of HIF-1α during intermittent hypoxia accounted for the higher resistance of endothelial cells. We also used an in vivo approach to enforce intermittent hypoxia in tumor-bearing mice and found that it was associated with less radiation-induced apoptosis within both the vascular and the tumor cell compartments (versus normoxia or prolonged hypoxia). Radioresistance was further ascertained by an increased rate of tumor regrowth in irradiated mice preexposed to intermittent hypoxia and confirmed in vitro using distinctly radiosensitive tumor cell lines. In conclusion, we have documented that intermittent hypoxia may condition endothelial cells and tumor cells in such a way that they are more resistant to apoptosis and more prone to participate in tumor progression. Our observations also underscore the potential of drugs targeting HIF-1α to resensitize the tumor vasculature to anticancer treatments. (Cancer Res 2006; 66(24): 11736-44)
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http://hdl.handle.net/2268/73972
also: http://hdl.handle.net/2268/17883

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