ArticlePloS one2015
OVCAR-3 spheroid-derived cells display distinct metabolic profiles.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 35 citations in OpenAlex.
- Paclitaxel resistance-associated metabolic events in ovarian cancer cells.Metabolomics : Official journal of the Metabolomic Society · 2025Article
- Targeting the glutamine-arginine-proline metabolism axis in cancer.Journal of enzyme inhibition and medicinal chemistry · 2024Review
- Integration of pan-omics technologies and three-dimensional in vitro tumor models: an approach toward drug discovery and precision medicine.Molecular cancer · 2024Review
- Comprehensive Two-Dimensional Gas Chromatography as a Bioanalytical Platform for Drug Discovery and Analysis.Pharmaceutics · 2023Review
- Safety assessment of cosmetics by read across applied to metabolomics data of in vitro skin and liver models.Archives of toxicology · 2021Article
- Metabolic Dynamics inACS synthetic biology · 2021Article
- Pyrroline-5-carboxylate reductase 1 (PYCR1) upregulation contributes to gastric cancer progression and indicates poor survival outcome.Annals of translational medicine · 2020Article
- Resolving Metabolic Heterogeneity in Experimental Models of the Tumor Microenvironment from a Stable Isotope Resolved Metabolomics Perspective.Metabolites · 2020Review
- Proline-Dependent Induction of Apoptosis in Oral Squamous Cell Carcinoma (OSCC)-The Effect of Celecoxib.Cancers · 2020Article
- Metabolomic Profile of Primary Turkey and Rat Hepatocytes and Two Cell Lines after Chloramphenicol Exposure.Animals : an open access journal from MDPI · 2019Article
- Metabolic Profiling ofIndustrial & engineering chemistry research · 2019Article
- Hypoxia-inducible factor-2α directly promotes BCRP expression and mediates the resistance of ovarian cancer stem cells to adriamycin.Molecular oncology · 2019Article
- Prediction of liver toxicity and mode of action using metabolomics in vitro in HepG2 cells.Archives of toxicology · 2018Article
- Metabolomics Analysis of the Toxic Effects of the Production of Lycopene and Its Precursors.Frontiers in microbiology · 2018Article
- The novel ZIP4 regulation and its role in ovarian cancer.Oncotarget · 2017Article
- Spheroid cancer stem cells display reprogrammed metabolism and obtain energy by actively running the tricarboxylic acid (TCA) cycle.Oncotarget · 2016Article
- Co-regulation of mitochondrial respiration by proline dehydrogenase/oxidase and succinate.Amino acids · 2016Article
- Proline biosynthesis augments tumor cell growth and aerobic glycolysis: involvement of pyridine nucleotides.Scientific reports · 2015Article
- Metabolomics identifies the intersection of phosphoethanolamine with menaquinone-triggered apoptosis in an in vitro model of leukemia.Molecular bioSystems · 2015Article
- Distinct metabolic responses of an ovarian cancer stem cell line.BMC systems biology · 2014Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionRecently, multicellular spheroids were isolated from a well-established epithelial ovarian cancer cell line, OVCAR-3, and were propagated in vitro. These spheroid-derived cells displayed numerous hallmarks of cancer stem cells, which are chemo- and radioresistant cells thought to be a significant cause of cancer recurrence and resultant mortality. Gene set enrichment analysis of expression data from the OVCAR-3 cells and the spheroid-derived putative cancer stem cells identified several metabolic pathways enriched in differentially expressed genes. Before this, there had been little previous knowledge or investigation of systems-scale metabolic differences between cancer cells and cancer stem cells, and no knowledge of such differences in ovarian cancer stem cells.
methodsTo determine if there were substantial metabolic changes corresponding with these transcriptional differences, we used two-dimensional gas chromatography coupled to mass spectrometry to measure the metabolite profiles of the two cell lines.
resultsThese two cell lines exhibited significant metabolic differences in both intracellular and extracellular metabolite measurements. Principal components analysis, an unsupervised dimensional reduction technique, showed complete separation between the two cell types based on their metabolite profiles. Pathway analysis of intracellular metabolomics data revealed close overlap with metabolic pathways identified from gene expression data, with four out of six pathways found enriched in gene-level analysis also enriched in metabolite-level analysis. Some of those pathways contained multiple metabolites that were individually statistically significantly different between the two cell lines, with one of the most broadly and consistently different pathways, arginine and proline metabolism, suggesting an interesting hypothesis about cancerous and stem-like metabolic phenotypes in this pair of cell lines.
conclusionsOverall, we demonstrate for the first time that metabolism in an ovarian cancer stem cell line is distinct from that of more differentiated isogenic cancer cells, supporting the potential importance of metabolism in the differences between cancer cells and cancer stem cells.
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