Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Isolation and characterization of stem-like cells from a human ovarian cancer cell line

ABSTRACT: Increasing evidence supports the existence of a subpopulation of cancer cells capable of self-renewal and differentiation into diverse cell lineages. These cancer stem-like or cancer initiating cells (CICs) also demonstrate resistance to chemo- and radiotherapy and may function as a primary source of cancer recurrence. We report here on the isolation and in vitro propagation of multicellular ovarian cancer spheroids from a well-established ovarian cancer cell line (OVCAR-3). Cells forming these spheroids display self-renewal potential, the ability to produce differentiated progeny and increased expression of genes previously associated with CICs. The spheroid-derived cells (SDCs) also demonstrate higher invasiveness, migration potential and enhanced resistance to standard anticancer agents relative to progenitor OVCAR-3 cells. SDCs display up-regulation of genes associated with epithelial-to-mesenchymal transitions (EMT), anticancer drug resistance and/or decreased susceptibility to apoptosis, as well as, down-regulation of genes typically associated with the epithelial cell phenotype and pro-apoptotic genes. Dataset includes 3 replicate cultures of parental OVCAR-3 cells and 3 replicate cultures of stem cell-like spheroid-derived cells

ORGANISM(S): Homo sapiens

SUBMITTER: Roman Mezencev

PROVIDER: E-GEOD-28799 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Recently, 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. To 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. These 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. Overall, 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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Isolation and characterization of stem-like cells from a human ovarian cancer cell line

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