ArticleThe Journal of clinical investigation2014
Mesothelial cells promote early ovarian cancer metastasis through fibronectin secretion.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 212 papers, 1 of them a synthesis that pooled it.
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Who cites it
212 citing papers in PubMed, 1 synthesis or guideline pooled it, 298 citations in OpenAlex.
- Mechanisms of Peritoneal Fibrosis: Focus on Immune Cells-Peritoneal Stroma Interactions.Frontiers in immunology · 2021Pooled it
- Exosome-Associated Proteins as Mediators and Biomarkers of Ovarian Cancer Dissemination.Biomolecules · 2026Review
- Cancer-associated mesothelial cells drive immune escape and therapy resistance in ovarian cancer.Journal for immunotherapy of cancer · 2026Article
- RelB drives integrin-mediated stress tolerance and relapse in high-grade serous ovarian cancer.Cell reports · 2026Article
- Cystathionine beta-synthase promotes anoikis resistance and transcoelomic metastasis in ovarian cancer via SP1- ITGB1 regulation.Experimental hematology & oncology · 2026Article
- Advanced 3D cancer models for analyzing tumor-immune cell interaction and therapeutic response.Molecular cancer · 2026Review
- Extracellular matrix polysaccharides and glycoproteins in ovarian cancer: structural-functional macromolecular perspectives and potential exosome-derived biomarkers.Cell communication and signaling : CCS · 2026Review
- PDK4-driven metabolic reprogramming enhances mesothelial cell invasion in colorectal cancer peritoneal metastasis.Acta biochimica et biophysica Sinica · 2026Article
- Mesothelial cells derived extracellular vesicles promote angiogenesis through the transfer of angiopoietin-2.PloS one · 2026Article
- Diversity within ovarian cancer subtypes and their tumor microenvironment.Frontiers in oncology · 2026Review
- Apoptosis of Mesothelial Cells Is Associated with the Pattern of Peritoneal Metastases in Ovarian Cancer.Cancers · 2025Article
- Article
- Spatial proteo-transcriptomic profiling reveals the molecular landscape of borderline ovarian tumors and their invasive progression.Cancer cell · 2025Article
- Navitoclax, a Bcl-2/xL Inhibitor, and YM155, a Survivin Inhibitor, in Combination with Carboplatin, Effectively Inhibit Ovarian Cancer Tumor Growth.Molecular cancer therapeutics · 2025Article
- Combined pharmacological targeting of CD9Cell reports. Medicine · 2025Article
- Interplay of integrins and selectins in metastasis.Molecular oncology · 2025Review
- Role of tumor microenvironment in ovarian cancer metastasis and clinical advancements.Journal of translational medicine · 2025Review
- The extracellular matrix protein type I collagen and fibronectin are regulated by β-arrestin-1/endothelin axis in human ovarian fibroblasts.Journal of experimental & clinical cancer research : CR · 2025Article
- Interleukin-6 Modulation in Ovarian Cancer Necessitates a Targeted Strategy: From the Approved to Emerging Therapies.Cancers · 2024Review
- Macrophage diversity in cancer dissemination and metastasis.Cellular & molecular immunology · 2024Review
152 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
Abstract
Ovarian cancer (OvCa) metastasizes to organs in the abdominal cavity, such as the omentum, which are covered by a single layer of mesothelial cells. Mesothelial cells are generally thought to be "bystanders" to the metastatic process and simply displaced by OvCa cells to access the submesothelial extracellular matrix. Here, using organotypic 3D cultures, we found that primary human mesothelial cells secrete fibronectin in the presence of OvCa cells. Moreover, we evaluated the tumor stroma of 108 human omental metastases and determined that fibronectin was consistently overexpressed in these patients. Blocking fibronectin production in primary mesothelial cells in vitro or in murine models, either genetically (fibronectin 1 floxed mouse model) or via siRNA, decreased adhesion, invasion, proliferation, and metastasis of OvCa cells. Using a coculture model, we determined that OvCa cells secrete TGF-β1, which in turn activates a TGF-β receptor/RAC1/SMAD-dependent signaling pathway in the mesothelial cells that promotes a mesenchymal phenotype and transcriptional upregulation of fibronectin. Additionally, blocking α5 or β1 integrin function with antibodies reduced metastasis in an orthotopic preclinical model of OvCa metastasis. These findings indicate that cancer-associated mesothelial cells promote colonization during the initial steps of OvCa metastasis and suggest that mesothelial cells actively contribute to metastasis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.