ArticleClinical & experimental metastasis2016
Mesothelial cells interact with tumor cells for the formation of ovarian cancer multicellular spheroids in peritoneal effusions.
Article in Clinical & experimental metastasis, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 46 citations in OpenAlex.
- Cystathionine beta-synthase promotes anoikis resistance and transcoelomic metastasis in ovarian cancer via SP1- ITGB1 regulation.Experimental hematology & oncology · 2026Article
- Positive ascites cytology in interval debulking surgery predicts poor outcomes of advanced epithelial ovarian cancer achieving complete tumor resection.Scientific reports · 2026Article
- Mesothelial cells promote peritoneal invasion and metastasis of ascites-derived ovarian cancer cells through spheroid formation.Science advances · 2026Article
- Harnessing ovarian cancer ascites for translational science: models, biomarkers, and therapeutics.Molecular cancer · 2025Review
- Morphometric analysis of neoplastic cell clusters in high-grade serous ovarian cancer ascites identifies a promising prognostic factor: a retrospective study.Journal of ovarian research · 2025Article
- Cisplatin resistance alters ovarian cancer spheroid formation and impacts peritoneal invasion.Frontiers in cell and developmental biology · 2025Article
- Crosstalk between stromal, immune, and ovarian cancer cells in lipid-rich tumor microenvironment exhibits proliferative features.Frontiers in immunology · 2025Review
- Beyond tumor‑associated macrophages involved in spheroid formation and dissemination: Novel insights for ovarian cancer therapy (Review).International journal of oncology · 2024Review
- Adipocyte derived exosomes promote cell invasion and challenge paclitaxel efficacy in ovarian cancer.Cell communication and signaling : CCS · 2024Article
- In Vitro Models of Ovarian Cancer: Bridging the Gap between Pathophysiology and Mechanistic Models.Biomolecules · 2023Review
- Immune Tumor Microenvironment in Ovarian Cancer Ascites.International journal of molecular sciences · 2022Review
- Spheroid Formation and Peritoneal Metastasis in Ovarian Cancer: The Role of Stromal and Immune Components.International journal of molecular sciences · 2022Review
- Metastatic Voyage of Ovarian Cancer Cells in Ascites with the Assistance of Various Cellular Components.International journal of molecular sciences · 2022Review
- Article
- Cancer-Associated Fibroblasts: Mechanisms of Tumor Progression and Novel Therapeutic Targets.Cancers · 2022Review
- Ovarian Cancer Cells in Ascites Form Aggregates That Display a Hybrid Epithelial-Mesenchymal Phenotype and Allows Survival and Proliferation of Metastasizing Cells.International journal of molecular sciences · 2022Article
- Multicellular Tumor Spheroids in Nanomedicine Research: A Perspective.Frontiers in medical technology · 2022Article
- Host Mesothelin Expression Increases Ovarian Cancer Metastasis in the Peritoneal Microenvironment.International journal of molecular sciences · 2021Article
- Multicellular Ovarian Cancer Model for Evaluation of Nanovector Delivery in Ascites and Metastatic Environments.Pharmaceutics · 2021Article
- The Detection of Stem-Like Circulating Tumor Cells Could Increase the Clinical Applicability of Liquid Biopsy in Ovarian Cancer.Life (Basel, Switzerland) · 2021Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epithelial ovarian cancer (EOC) dissemination is primarily mediated by the shedding of tumor cells from the primary site into ascites where they form multicellular spheroids that rapidly lead to peritoneal carcinomatosis. While the clinical importance and fundamental role of multicellular spheroids in EOC is increasingly appreciated, the mechanisms that regulate their formation and dictate their cellular composition remain poorly characterized. To investigate these important questions, we characterized spheroids isolated from ascites of women with EOC. We found that in these spheroids, a core of mesothelial cells was encased in a shell of tumor cells. Analysis further revealed that EOC spheroids are dynamic structures of proliferating, non-proliferating and hypoxic regions. To recapitulate these in vivo findings, we developed a three-dimensional co-culture model of primary EOC and mesothelial cells. Our analysis indicated that, compared to the OVCAR3 cell line, primary EOC cells isolated from ascites as well as mesothelial cells formed compact spheroids. Analysis of heterotypic spheroid microarchitecture revealed a structure that grossly resembles the structure of spheroids isolated from ascites. Cells that formed compact spheroids had elevated expression of β1 integrin and low expression of E-cadherin. Addition of β1 integrin blocking antibody or siRNA-mediated downregulation of β1 integrin resulted in reduced tightness of the spheroids. Interestingly, the loss of MUC16 and E-cadherin expression resulted in the formation of more compact spheroids. Therefore, our findings support the heterotypic nature of spheroids from malignant EOC ascites. In addition, our data describe an unusual link between E-cadherin expression and less compact spheroids. Our data also emphasize the role of MUC16 and β1 integrin in EOC spheroid formation.
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