title: Cancer stem cells from epithelial ovarian cancer patients privilege oxidative phosphorylation, and resist glucose deprivation.
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.
authors.affiliation: Department of Surgery, Oncology, and Gastroenterology, Oncology Section, University of Padova, Padova, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Pastò
authors.forename: Chiara
authors.initials: C
authors.lastname: Bellio
authors.forename: Giorgia
authors.initials: G
authors.lastname: Pilotto
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Ciminale
authors.forename: Micol
authors.initials: M
authors.lastname: Silic-Benussi
authors.forename: Giulia
authors.initials: G
authors.lastname: Guzzo
authors.forename: Andrea
authors.initials: A
authors.lastname: Rasola
authors.forename: Chiara
authors.initials: C
authors.lastname: Frasson
authors.forename: Giorgia
authors.initials: G
authors.lastname: Nardo
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Zulato
authors.forename: Maria Ornella
authors.initials: MO
authors.lastname: Nicoletto
authors.forename: Mariangela
authors.initials: M
authors.lastname: Manicone
authors.forename: Stefano
authors.initials: S
authors.lastname: Indraccolo
authors.forename: Alberto
authors.initials: A
authors.lastname: Amadori
mesh_terms: D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D018613:Microscopy, Confocal; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism*; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation
chemical_list: D005947:Glucose