title: Reprogramming of tumor metabolism by targeting mitochondria improves tumor response to irradiation.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center for Molecular Imaging, Radiotherapy and Oncology, Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain (UCL) , Brussels , Belgium.
authors.forename: Vanesa
authors.initials: V
authors.lastname: Bol
authors.forename: Anne
authors.initials: A
authors.lastname: Bol
authors.forename: Caroline
authors.initials: C
authors.lastname: Bouzin
authors.forename: Daniel
authors.initials: D
authors.lastname: Labar
authors.forename: John A
authors.initials: JA
authors.lastname: Lee
authors.forename: Guillaume
authors.initials: G
authors.lastname: Janssens
authors.forename: Paolo E
authors.initials: PE
authors.lastname: Porporato
authors.forename: Pierre
authors.initials: P
authors.lastname: Sonveaux
authors.forename: Olivier
authors.initials: O
authors.lastname: Feron
authors.forename: Vincent
authors.initials: V
authors.lastname: Grégoire
mesh_terms: D000332:Aerobiosis; D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D045744:Cell Line, Tumor; D002470:Cell Survival; D004260:DNA Repair; D005260:Female; D006019:Glycolysis / Q000502:physiology*; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008928:Mitochondria / Q000502:physiology*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D010101:Oxygen Consumption / Q000502:physiology*; D010641:Phenotype; D011836:Radiation Tolerance / Q000502:physiology*
chemical_list: D006657:Histones; C475961:gamma-H2AX protein, mouse