title: Distinct metabolic responses of an ovarian cancer stem cell line.
abstract: BACKGROUND
  Cancer metabolism is emerging as an important focus area in cancer research. However, the in vitro cell culture conditions under which much cellular metabolism research is performed differ drastically from in vivo tumor conditions, which are characterized by variations in the levels of oxygen, nutrients like glucose, and other molecules like chemotherapeutics. Moreover, it is important to know how the diverse cell types in a tumor, including cancer stem cells that are believed to be a major cause of cancer recurrence, respond to these variations. Here, in vitro environmental perturbations designed to mimic different aspects of the in vivo environment were used to characterize how an ovarian cancer cell line and its derived, isogenic cancer stem cells metabolically respond to environmental cues.
  
  
  RESULTS
  Mass spectrometry was used to profile metabolite levels in response to in vitro environmental perturbations. Docetaxel, the chemotherapeutic used for this experiment, caused significant metabolic changes in amino acid and carbohydrate metabolism in ovarian cancer cells, but had virtually no metabolic effect on isogenic ovarian cancer stem cells. Glucose deprivation, hypoxia, and the combination thereof altered ovarian cancer cell and cancer stem cell metabolism to varying extents for the two cell types. Hypoxia had a much larger effect on ovarian cancer cell metabolism, while glucose deprivation had a greater effect on ovarian cancer stem cell metabolism. Core metabolites and pathways affected by these perturbations were identified, along with pathways that were unique to cell types or perturbations.
  
  
  CONCLUSIONS
  The metabolic responses of an ovarian cancer cell line and its derived isogenic cancer stem cells differ greatly under most conditions, suggesting that these two cell types may behave quite differently in an in vivo tumor microenvironment. While cancer metabolism and cancer stem cells are each promising potential therapeutic targets, such varied behaviors in vivo would need to be considered in the design and early testing of such treatments.
authors.affiliation: School of Chemical & Biomolecular Engineering and Parker H. Petit Institute for Bioengineering & Bioscience, Georgia Institute of Technology, 311 Ferst Dr, Atlanta, GA, 30332-0100, USA. kvermeersch@gatech.edu.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Vermeersch
authors.affiliation: Ovarian Cancer Institute, School of Biology, and Parker H. Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, 315 Ferst Dr, Atlanta, GA, 30332-0363, USA. lijuan.wang@biology.gatech.edu.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Ovarian Cancer Institute, School of Biology, and Parker H. Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, 315 Ferst Dr, Atlanta, GA, 30332-0363, USA. john.mcdonald@biology.gatech.edu.
authors.forename: John F
authors.initials: JF
authors.lastname: McDonald
authors.affiliation: School of Chemical & Biomolecular Engineering and Parker H. Petit Institute for Bioengineering & Bioscience, Georgia Institute of Technology, 311 Ferst Dr, Atlanta, GA, 30332-0100, USA. Mark.Styczynski@chbe.gatech.edu.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Styczynski
mesh_terms: D015687:Cell Hypoxia / Q000502:physiology*; D045744:Cell Line, Tumor; D000077143:Docetaxel; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D013058:Mass Spectrometry; D053858:Metabolic Networks and Pathways / Q000502:physiology*; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism*; D025341:Principal Component Analysis; D043823:Taxoids / Q000494:pharmacology*; D059016:Tumor Microenvironment
chemical_list: D043823:Taxoids; D000077143:Docetaxel