TY - JOUR
T1 - Cancer stem cells from epithelial ovarian cancer patients privilege oxidative phosphorylation, and resist glucose deprivation
AU - Pastò, Anna
AU - Bellio, Chiara
AU - Pilotto, Giorgia
AU - Ciminale, Vincenzo
AU - Silic-Benussi, Micol
AU - Guzzo, Giulia
AU - Rasola, Andrea
AU - Frasson, Chiara
AU - Nardo, Giorgia
AU - Zulato, Elisabetta
AU - Nicoletto, Maria Ornella
AU - Manicone, Mariangela
AU - Indraccolo, Stefano
AU - Amadori, Alberto
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Cancer stem cells
KW - Glucose
KW - Metabolism
KW - Ovarian cancer
KW - Warburg effect
UR - http://www.scopus.com/inward/record.url?scp=84905118703&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84905118703&partnerID=8YFLogxK
M3 - Article
C2 - 24946808
AN - SCOPUS:84905118703
VL - 5
SP - 4305
EP - 4319
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 12
ER -