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

doi:10.18632/oncotarget.2010

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Research Papers:

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 and Alberto Amadori _

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Oncotarget. 2014; 5:4305-4319. https://doi.org/10.18632/oncotarget.2010

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Abstract

Anna Pastò1,*, Chiara Bellio1,*, Giorgia Pilotto1,*, Vincenzo Ciminale1,2, Micol Silic-Benussi2, Giulia Guzzo3, Andrea Rasola3, Chiara Frasson4, Giorgia Nardo2, Elisabetta Zulato2, Maria Ornella Nicoletto2, Mariangela Manicone2, Stefano Indraccolo2,* and Alberto Amadori1,2,*

1 Department of Surgery, Oncology, and Gastroenterology, Oncology Section, University of Padova, Padova, Italy

2 Istituto Oncologico Veneto-IRCCS (IOV), Padova, Italy

3 Department of Biomedical Sciences, University of Padova, Padova, Italy

4 Department of Woman and Child Health, Laboratory of Hemato-Oncology, University of Padova, Padova, Italy

* These Authors contributed equally to this work

Correspondence:

Alberto Amadori, email:

Keywords: Ovarian cancer, Cancer Stem Cells, metabolism, glucose, Warburg effect

Received: February 27, 2014 Accepted: May 24, 2014 Published: May 26, 2014

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.

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Research Papers:

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

Abstract