ArticleGastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association2018
Importance of human peritoneal mesothelial cells in the progression, fibrosis, and control of gastric cancer: inhibition of growth and fibrosis by tranilast.
Article in Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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36 citing papers in PubMed, 50 citations in OpenAlex.
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- Gastric Cancer: Pathobiology and Therapeutics.MedComm · 2026Review
- Advances and challenges in the application of prophylactic hyperthermic intraperitoneal chemotherapy for gastric cancer.Frontiers in oncology · 2026Review
- Optimized Method for Establishing Primary Human Mesothelial Cell Cultures Preserving Epithelial Phenotype.Biomolecules · 2025Article
- Targeting inflammasomes as an immunotherapeutic strategy for cancer.Journal of translational medicine · 2025Review
- Advances in Intraperitoneal Chemotherapy for Gastric Cancer Patients with Peritoneal Metastases: Current Status of Treatment and Institutional Insights.Journal of clinical medicine · 2025Article
- Molecular mechanisms of metastatic peritoneal dissemination in gastric adenocarcinoma.Cancer metastasis reviews · 2025Review
- The Role of the Tumor Microenvironment (TME) in Advancing Cancer Therapies: Immune System Interactions, Tumor-Infiltrating Lymphocytes (TILs), and the Role of Exosomes and Inflammasomes.International journal of molecular sciences · 2025Review
- Metastasis-associated fibroblasts in peritoneal surface malignancies.British journal of cancer · 2024Review
- The 'speck'-tacular oversight of the NLRP3-pyroptosis pathway on gastrointestinal inflammatory diseases and tumorigenesis.Journal of biomedical science · 2023Review
- Intraperitoneal transfer of microRNA-29b-containing small extracellular vesicles can suppress peritoneal metastases of gastric cancer.Cancer science · 2023Article
- Galectin-1 promotes gastric cancer peritoneal metastasis through peritoneal fibrosis.BMC cancer · 2023Article
- Involvement of inflammasomes in tumor microenvironment and tumor therapies.Journal of hematology & oncology · 2023Review
- Adipocytes contribute to tumor progression and invasion of peritoneal metastasis by interacting with gastric cancer cells as cancer associated fibroblasts.Cancer reports (Hoboken, N.J.) · 2023Article
- CXCL8 and the peritoneal metastasis of ovarian and gastric cancer.Frontiers in immunology · 2023Review
- Signaling pathways and therapeutic interventions in gastric cancer.Signal transduction and targeted therapy · 2022Review
- Drug repositioning of tranilast to sensitize a cancer therapy by targeting cancer-associated fibroblast.Cancer science · 2022Article
- Crosstalk between cancer-associated fibroblasts and immune cells in peritoneal metastasis: inhibition in the migration of M2 macrophages and mast cells by Tranilast.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2022Article
- MiR-29b may suppresses peritoneal metastases through inhibition of the mesothelial-mesenchymal transition (MMT) of human peritoneal mesothelial cells.Scientific reports · 2022Article
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Authors and funding
11 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundScirrhous gastric cancer is an intractable disease with a high incidence of peritoneal dissemination and obstructive symptoms (e.g., ileus, jaundice, and hydronephrosis) arising from accompanying marked fibrosis. Microenvironmental interactions between cancer cells and cancer-associated fibroblasts are the suggested cause of the disease. We elucidated the mechanisms of tumor growth and fibrosis using human peritoneal mesothelial cells (HPMCs) and investigated the effects of tranilast treatment on cells and a xenograft mouse model of fibrosis.
methodsHPMCs were isolated from surgically excised omentum and their interaction with MKN-45 gastric cancer cells was investigated using co-culture. Furthermore, a fibrosis tumor model was developed based on subcutaneous transplantation of co-cultured cells into the dorsal side of nude mice to form large fibrotic tumors. Mice were subsequently treated with or without tranilast.
resultsThe morphology of HPMCs treated with transforming growth factor (TGF)-β1 changed from cobblestone to spindle-type. Moreover, E-cadherin was weakly expressed whereas high levels of α-smooth muscle actin expression were observed. TGF-β-mediated epithelial-mesenchymal transition-like changes in HPMCs were inhibited in a dose-dependent manner following tranilast treatment through inhibition of Smad2 phosphorylation. In the mouse model, tumor size decreased significantly and fibrosis was inhibited in the tranilast treatment group compared with that in the control group.
conclusionsTranilast acts on the TGF-β/Smad pathway to inhibit interactions between cancer cells and cancer-associated fibroblasts, thereby inhibiting tumor growth and fibrosis. This study supports the hypothesis that tranilast represents a novel strategy to prevent fibrous tumor establishment represented by peritoneal dissemination.
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