Journal
ONCOTARGET
Volume 5, Issue 12, Pages 4305-4319Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.2010
Keywords
Ovarian cancer; Cancer Stem Cells; metabolism; glucose; Warburg effect
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Funding
- Italian Association for Cancer Research (AIRC)
- Ministry of University and Research
- University of Padova
- AIRC
- IOV
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We investigated the metabolic profile of cancer stem cells (CSC) isolated from patients with epithelial ovarian cancer. CSC overexpressed genes associated with glucose uptake, oxidative phosphorylation (OXPHOS), and fatty acid beta-oxidation, indicating higher ability to direct pyruvate towards the Krebs cycle. Consistent with a metabolic profile dominated by OXPHOS, the CSC showed higher mitochondrial reactive oxygen species (ROS) production and elevated membrane potential, and underwent apoptosis upon inhibition of the mitochondrial respiratory chain. The CSC also had a high rate of pentose phosphate pathway (PPP) activity, which is not typical of cells privileging OXPHOS over glycolysis, and may rather reflect the PPP role in recharging scavenging enzymes. Furthermore, CSC resisted in vitro and in vivo glucose deprivation, while maintaining their CSC phenotype and OXPHOS profile. These observations may explain the CSC resistance to anti-angiogenic therapies, and indicate this peculiar metabolic profile as a possible target of novel treatment strategies.
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