title: 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). The spheroid-derived cells (SDCs) display self-renewal potential, the ability to produce differentiated progeny, and increased expression of genes previously associated with CICs. SDCs also demonstrate higher invasiveness, migration potential, and enhanced resistance to standard anticancer agents relative to parental OVCAR-3 cells. Furthermore, SDCs display up-regulation of genes associated with epithelial-to-mesenchymal transition (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. Pathway and biological process enrichment analyses indicate significant differences between the SDCs and precursor OVCAR-3 cells in TGF-beta-dependent induction of EMT, regulation of lipid metabolism, NOTCH and Hedgehog signaling. Collectively, our results indicate that these SDCs will be a useful model for the study of ovarian CICs and for the development of novel CIC-targeted therapies.
authors.affiliation: Ovarian Cancer Institute and School of Biology, Georgia Institute of Technology, 315 Ferst Dr, Atlanta, GA 30332-0363, USA.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Wang
authors.forename: Roman
authors.initials: R
authors.lastname: Mezencev
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Bowen
authors.forename: Lilya V
authors.initials: LV
authors.lastname: Matyunina
authors.forename: John F
authors.initials: JF
authors.lastname: McDonald
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002469:Cell Separation / Q000379:methods; D002470:Cell Survival / Q000187:drug effects; D016000:Cluster Analysis; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D015398:Signal Transduction; D018874:Spheroids, Cellular
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor