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Reprogramming of tumor metabolism by targeting mitochondria improves tumor response to irradiation.

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Bol, Vanesa [UCL] Bol, Anne [UCL] Bouzin, Caroline [UCL] Labar, Daniel [UCL] Lee, John Aldo [UCL] Porporato, Paolo [UCL] Sonveaux, Pierre [UCL] Feron, Olivier [UCL] Grégoire, Vincent

Background. The Warburg phenotype identified decades ago describes tumor cells with increased glycolysis and decreased mitochondrial respiration even in the presence of oxygen. This particular metabolism also termed 'aerobic glycolysis' reflects an adaptation of tumor cells to proliferation in a heterogeneous tumor microenvironment. Although metabolic alterations in cancer cells are common features, their impact on the response to radiotherapy is not yet fully elucidated. This study investigated the impact of cellular oxygen consumption inhibition on the tumor response to radiotherapy. Material and methods. Warburg-phenotype tumor cells with impaired mitochondrial respiration (MD) were produced and compared in respect to their metabolism to the genetically matched parental cells (WT). After characterization of their metabolism we compared the response of MD cells to irradiation in vivo and in vitro to the genetically matched parental cells (WT). Results. We first confirmed that MD cells were exclusively glycolytic while WT cells exhibited mitochondrial respiration. We then used these cells for assessing the response of WT and MD tumors to a single dose of radiation and showed that the in vivo tumor growth delay of the MD group was increased, indicating an increased radiosensitivity compared to WT while the in vitro ability of both cell lines to repair radiation-induced DNA damage was similar. Conclusion. Taken together, these results indicate that in addition to intrinsic radiosensitivity parameters the tumor response to radiation will also depend on their metabolic rate of oxygen consumption.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès interdit
Publication date 2014
Language Anglais
Journal information "Acta Oncologica" - Vol. 54, no. 2, p. 266-274 (2015)
Peer reviewed yes
Publisher Informa Healthcare (London)
issn 0284-186X
e-issn 1651-226X
Publication status Publié
Affiliations UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie
UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique
UCL - SSS/IREC - Institut de recherche expérimentale et clinique
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Bibliographic reference Bol, Vanesa ; Bol, Anne ; Bouzin, Caroline ; Labar, Daniel ; Lee, John Aldo ; et. al. Reprogramming of tumor metabolism by targeting mitochondria improves tumor response to irradiation.. In: Acta Oncologica, Vol. 54, no. 2, p. 266-274 (2015)
Permanent URL http://hdl.handle.net/2078.1/147346