An experimental model for ovarian cancer: Propagation of ovarian cancer initiating cells and generation of ovarian cancer organoids
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PROVIDER: PRJNA830350 | ENA |
REPOSITORIES: ENA
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Project description:To establish an iOCIC model, an high-grade serous ovarian cancer (HGSOC) cell line, OVCAR-3 was reprogrammed by transducing Yamanaka four factors OCT4, SOX2, KLF4 and MYC (OSKM) We then performed gene expression profiling analysis using data obtained from RNA-seq of 3 different cells.
2022-09-20 | GSE201206 | GEO
Project description:BackgroundOvarian cancer (OC) is the most lethal gynecological cancer due to the recurrence of drug-resistance. Cancer initiating cells (CICs) are proposed to be responsible for the aggressiveness of OC. The rarity and difficulty of in vitro long-term cultivation of CICs challenge the development of CIC-targeting therapeutics. Reprogramming cancer cells into induced cancer initiating cell (iCICs) could be an approach to solve these. Several inducible CICs have been acquired by activating the expression of stemness genes in different cancer cells. However, few reports have demonstrated the feasibility in OC.MethodsPatients with primary OC receiving surgery were enrolled. Tumor tissue were collected, and OCT4, SOX2, and NANOG expressions were assessed by immunohistochemistry (IHC) staining to investigate the association of stemness markers with overall survival (OS). An high-grade serous ovarian cancer (HGSOC) cell line, OVCAR-3 was reprogrammed by transducing Yamanaka four factors OCT4, SOX2, KLF4 and MYC (OSKM) to establish an iOCIC model, iOVCAR-3-OSKM. CIC characteristics of iOVCAR-3-OSKM were evaluated by RT-PCR, sphere formation assay and animal experiments. Drug-resistance and migration ability were accessed by dye-efflux activity assay, MTT assay and migration assay. Gene profile was presented through RNA-sequencing. Lineage differentiation ability and organoid culture were determined by in vitro differentiation assays.ResultsIn OC patients, the co-expression of multiple stem-related transcription factors (OCT4, SOX2, and NANOG) was associated with worse OS. iOVCAR-3-OSKM cells generated by reprogramming successfully exhibited stemness characteristics with strong sphere-forming and tumorigenesis ability. iOVCAR-3-OSKM cells also showed malignant potential with higher drug resistance to chemodrug, Paclitaxel (PTX) and migration ability. iOVCAR-3-OSKM was maintainable and expandable on feeder-dependent culture condition, it also preserved ovarian lineage differentiation abilities, which could well differentiate into OC cells with CK-7 and CA125 expressions and develop into an organoid mimic poor prognostic OC histological feature.ConclusionsThe establishment of iOVCAR-3-OSKM not only allows us to fill the gap in the information on induced CICs in OC but also provides a potential strategy to develop personalized CICs and organoid models for treating OC in the near future.
| S-EPMC9463800 | biostudies-literature
Project description:The gene expression profile in treated CP70 side population spheroid cells (CP70sps cells) was analyzed to investigate the effect of niclosamide inhibition on ovarian tumor-initiating cells. CP70sps cells are isolated and characterized as one kind of ovarian tumor-initiating cells, and they show stemness properties and drug resistance capacity. According gene expression profiles and mechanistic analysis, all evidences revealed niclosamide disrupted multiple metabolic pathways affecting biogenetics, biogenesis and redox regulation. These studies support niclosamide as a promising therapeutic agent for ovarian cancer.
2012-08-06 | GSE36259 | GEO
Project description:The gene expression profile in treated CP70 side population spheroid cells (CP70sps cells) was analyzed to investigate the effect of niclosamide inhibition on ovarian tumor-initiating cells. CP70sps cells are isolated and characterized as one kind of ovarian tumor-initiating cells, and they show stemness properties and drug resistance capacity. According gene expression profiles and mechanistic analysis, all evidences revealed niclosamide disrupted multiple metabolic pathways affecting biogenetics, biogenesis and redox regulation. These studies support niclosamide as a promising therapeutic agent for ovarian cancer. CP70sps cells were treated with niclosamide for 0, 2, 4 and 6 hours respectively, and then cells were harvested and analyzed their gene expression profiles.
2012-08-05 | E-GEOD-36259 | biostudies-arrayexpress
Project description: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
2011-04-23 | E-GEOD-28799 | biostudies-arrayexpress
Project description:Different cellular compartments within a tissue present distinct cancer-initiating capacity. Current approach to dissect cellular heterogeneity in cancer-initiating capacity requires a well-understood tissue lineage hierarchy and highly-specific promoters, which are lacking for most tissues. Here, utilizing a genetic tool called Mosaic Analysis with Double Markers (MADM), we induced scattered GFP-labeled single mutant cells in a broad category of cell types and quantitatively traced their expansion at clonal level, to pinpoint cells susceptible for cancer initiation within under-defined tissues. We dissected the heterogeneous cancer-initiating capacity of fallopian tube Pax8+ cells, which are thought to be the origin for high-grade serous ovarian cancer. We revealed that only a rare primitive subset enriched in the fimbriae can fuel ovarian cancer initiation, and oncogenic mutations exaggerate their intrinsic potential and bias their differentiation for further progression. Collectively, we demonstrated a scheme to dissect cellular heterogeneity in cancer-initiating capacity in tissues lacking established lineage hierarchy.
2022-08-06 | GSE210409 | GEO
Project description:The differentiation of stem-like cells of tumors may contribute to the cellular heterogeneity of breast cancers. We report the propagation of highly enriched mouse mammary cancer stem cells that retain the potential to differentiate both in vivo and in culture and their use to identify chemical compounds that influence both self-renewal and differentiation. We identify epithelial tumor initiating cells (ETIC) that expresses lineage markers of both basal and luminal mammary cell lineages and retains the potential to generate heterogeneous tumors similar to the tumor of origin from even single cells. ETIC can progress through a Rho associated coil-coil protein kinase 1 (ROCK1) dependent, epithelial to mesenchymal transition to generate a second cell type capable of initiating tumors of limited heterogeneity. The propagation of ETIC will increase the opportunities for identifying new therapeutic compounds that may inhibit or prevent progression of some types of breast cancer. These data compare the gene expression pattern of ETIC and MTIC. Total RNA obtained from ETIC and MTIC cells, allowing the comparison of gene expression patterns and the selection of potential targets.
2012-09-01 | E-GEOD-33433 | biostudies-arrayexpress
Project description:Breast Cancer Initiating Cells RNA-seq
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Project description:Transcriptional profiling of induced ovarian cancer initiating cell comparing control untransfected OVCAR-3 cells with iOVCAR-3 cells transfected with OCT3/4, SOX2, KLF4, and c-MYC genes. The aim of this study is to generate an induced ovarian cancer initiating cell (iOCICs) model by transducing defined factors into an OC cell line.
2023-11-14 | GSE161488 | GEO