ArticleBMC cancer2022
An experimental model for ovarian cancer: propagation of ovarian cancer initiating cells and generation of ovarian cancer organoids.
Article in BMC cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 13 citations in OpenAlex.
- Integrated molecular subtyping and functional analysis of circ_0001946/miR-7-5p axis reveals a glucose metabolism-linked regulatory mechanism in ovarian cancer.World journal of surgical oncology · 2025Article
- AAV for ovarian cancer gene therapy.Cancer gene therapy · 2025Review
- Organoid development and applications in gynecological cancers: the new stage of tumor treatment.Journal of nanobiotechnology · 2025Review
- Development and Application of Tumor Organoids: An Emerging Platform for Gynecological Cancers.International journal of women's health · 2025Review
- The role of cytostatic in oxidative stress reactions.Frontiers in oncology · 2025Review
- Prognostic Protein Biomarker Screening for Thyroid Carcinoma Based on Cancer Proteomics Profiles.Biomedicines · 2024Article
- The occurrence and development of induced pluripotent stem cells.Frontiers in genetics · 2024Review
- Patient-Derived Organoids: The Beginning of a New Era in Ovarian Cancer Disease Modeling and Drug Sensitivity Testing.Biomedicines · 2022Review
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
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.
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