Cancer stem cells from epithelial ovarian cancer patients privilege oxidative phosphorylation, and resist glucose deprivation

Anna Pastò, Chiara Bellio, Giorgia Pilotto, Vincenzo Ciminale, Micol Silic-Benussi, Giulia Guzzo, Andrea Rasola, Chiara Frasson, Giorgia Nardo, Elisabetta Zulato, Maria Ornella Nicoletto, Mariangela Manicone, Stefano Indraccolo, Alberto Amadori

Research output: Contribution to journalArticlepeer-review

Abstract

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 β-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.

Original languageEnglish
Pages (from-to)4305-4319
Number of pages15
JournalOncotarget
Volume5
Issue number12
Publication statusPublished - 2014

Keywords

  • Cancer stem cells
  • Glucose
  • Metabolism
  • Ovarian cancer
  • Warburg effect

ASJC Scopus subject areas

  • Oncology
  • Medicine(all)

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