Exploiting cancer dormancy signaling mechanisms in epithelial ovarian cancer through spheroid and organoid analysis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1199445 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Epithelial ovarian cancer (EOC) exhibits a unique mode of metastasis, involving spheroid formation in the peritoneum. Our research on EOC spheroid cell biology has provided valuable insights into the signalling plasticity associated with metastasis. We speculate that EOC cells modify their biology between tumor and spheroid states during cancer dormancy, although the specific mechanisms underlying this transition remain unknown. Here, we present novel findings from direct comparisons between cultured EOC spheroids and organoids. Our results indicated that AMP-activated protein kinase (AMPK) activity was significantly upregulated and protein kinase B (Akt) was downregulated in iOvCa spheroids compared to organoids, suggesting a clear differential phenotype. Through a comprehensive RNA sequencing analysis, we further supported these phenotypic differences and highlighted the significance of cell cycle regulation in organoids. By inhibiting the G2/M checkpoint via kinase inhibitors, we confirmed that this pathway is essential for organoids. Interestingly, our results suggest that specifically targeting aurora kinase A (AURKA) may represent a promising therapeutic strategy since our cells were equally sensitive to Alisertib treatment as both spheroids and organoids. Our findings emphasize the importance of studying cellular adaptations of EOC cells, as there may be different therapeutic targets depending on the step of EOC disease progression.
2025-01-29 | GSE284507 | GEO
Project description:Purpose: To understand the changes in RNA expression in tumor-initiating cell (TIC) (spheroid) and non-TIC populations (adherent) in ovarian cancer. Methods: OV90 cells were grown in adherent (non-TIC) or spheroid (TIC) conditions. Total RNA was extracted from each condition and RNAseq was performed and analysed for differential gene expression between the conditions.
2020-10-03 | GSE158949 | GEO
Project description:Using a novel platform based on the findings that Pluronic F-127 (PF-127) could trigger highly uniform spheroid assembly, we develop a one-pot organoid differentiation strategy. Using our strategy, we successfully generate cortical, nephron, hepatic, and lung organoids with improved reproducibility compared to previous methods while reducing the original costs by 80-95%. In addition, we adapt our platform to microfluidic chips allowing automated culture. We showcase that our platform can be applied to tissue-specific screening, such as drug toxicity and transfection reagents testing. And, we generate NEAT1 knockout tissue-specific organoids and show NEAT1 modulates multiple signaling pathways fine-tuning the differentiation of nephron and hepatic organoids and suppresses immune responses in cortical organoids. In summary, our strategy provides a powerful platform for advancing organoid research and studying human development and diseases.
2023-08-08 | GSE240256 | GEO
Project description:Introduction: In vitro 3-dimension spheroid culture has been widely used as model to enrich CD44+CD24dim/- cancer stem cells with high ALDH1 activity. However, present of the CD24+ population in the 3D spheroid also requests further attention as this side-population of cells may response differently to drug treatment comparing to the cancer stem cells. Methods: In this study, CD24+ population from the MCF-7 spheroid was sorted and subjected to spheroid formation test, stem cell markers immunofluorescence, invasion/migration test, and microRNA expression profiling. MCF-7 CD24+ cells sorted from primary spheroid reform 3D spheroid after longer period of time associated with dim expression of surface SOX-2, CD44, CD49f and Nanog comparing to the primary spheroid. Results: Remarkably, the MCF-7 CD24+ cells was found with high expression of ALDH1 protein, which subsequently contributed to higher resistant against doxorubicin and cisplatin. MicroRNA profiling has shown that absent of cancer stem cell phenotypes were contributed by the downregulation of major cancer stem cells related pathways including Hedgehog, Wnt and MAPK signalling pathways. Besides, resistance of CD24+ cells was correlated to dyregulation of cell death pathway.
2018-03-12 | GSE95598 | GEO
Project description:Immortal spheroids were generated from fetal mouse intestine using the culture system developed to culture organoids from adult intestinal epithelium. Spheroids are made of a monostratified polarized epithelium displaying a poorly differentiated intestinal phenotype. The proportion of spheroids generated from intestinal explants progressively decreases from fetal to postnatal period, with a corresponding increase in production of organoids. Spheroid cells show indefinite self-renewing properties but exhibit a transcriptome strikingly different from that of adult intestinal stem cells reminiscent of incompletely caudalized progenitors. The receptor Lgr4, but not Lgr5, is essential for their growth. Trop2/Tacstd2 and Cnx43/Gja1, two markers highly enriched in spheroids, are expressed throughout the E14 intestinal epithelium. Comparison of in utero and neonatal lineage tracing using Cnx43-CreER and Lgr5-CreERT2 mice identified spheroid-generating cells as developmental progenitors involved in generation of the prenatal intestinal epithelium. Ex vivo, spheroid cells have the potential to differentiate into organoids, thus qualifying them as a new type of intestinal stem-like cells. Two-channel microarray experiments were performed from spheroid/organoid pairs isolated each from a given embryo. Following initial seeding of small intestine from a given embryo/mouse (at E16, E18 or P0), spheroids and organoids were selectively picked up for each animal and replated for 3 passages to reach sample homogeneity. Hybridization was performed on the 4 independent pairs with dye-swap.
2014-01-21 | E-GEOD-49803 | biostudies-arrayexpress
Project description:Purpose: Treatment-induced tumor dormancy is a state in cancer progression where residual disease is present but remains asymptomatic. Dormant cancer cells are treatment-resistant and responsible for cancer recurrence and metastasis. Prostate cancer (PCa) treated with androgen-deprivation therapy (ADT) often enters a dormant state. ADT-induced PCa dormancy remains poorly understood due to the challenge in acquiring clinical dormant PCa cells and the lack of representative models. We, therefore, aimed to develop clinically relevant models that can be used for studying ADT-induced PCa dormancy. Experimental design: Dormant PCa models were established by castrating mice bearing PCa patient-derived xenografts (PDXs) of hormonal naïve or sensitive PCa. Dormancy status and tumor relapse were monitored and evaluated. Paired pre- and post-castration (dormant) PDX tissues were subjected to morphological and transcriptome profiling analyses. Results: We established eleven ADT-induced dormant PCa models that closely mimicked the clinical courses of ADT-treated PCa. We identified two ADT-induced dormancy subtypes that differed in morphology, gene expression, and relapse rates. We discovered transcriptomic differences in pre-castration PDXs that predisposed the dormancy response to ADT. We further developed a dormancy subtype-based, predisposed gene signature that was significantly associated with ADT response in hormonal naïve PCa and clinical outcome in castration-resistant PCa treated with ADT or androgen-receptor pathway inhibitors.
2022-01-11 | GSE193500 | GEO
Project description:Patient-derived breast cancer organoid study
| PRJNA786253 | ENA
Project description:Patient-derived breast cancer organoid study
| PRJNA786254 | ENA
Project description:L-OHP resistant gastric cancer organoid
| PRJNA1180444 | ENA