ArticlePloS one2013
Interleukin-6 mediates epithelial-stromal interactions and promotes gastric tumorigenesis.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
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Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.
- Overlapping cytokines inFrontiers in immunology · 2023Pooled it
- Hepatic origin of increased serum TFF3 in gastric cancer bearing subjects.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2026Article
- Gastric Cancer: Pathobiology and Therapeutics.MedComm · 2026Review
- Research progress on the correlation between OPN and immune escape of gastric cancer.Clinical and experimental medicine · 2026Review
- Tight junction proteins: Gatekeepers turned facilitators in the pathogenesis of gastric adenocarcinoma.World journal of gastrointestinal oncology · 2026Review
- The central role of IL-6 in the differential effects of GLP-1 receptor agonists and metformin across multiple health conditions.Frontiers in immunology · 2026Review
- Crucial role of IL-6, IL-8, IL-11 and leptin in tumor microenvironment in a group of patients with GEP-NETs- crosstalk between inflammation and cancer.Frontiers in endocrinology · 2026Article
- Inflammation and detection: Rethinking the biomarker landscape in gastric cancer.World journal of clinical oncology · 2025Article
- Serum pro-inflammatory cytokines as potential biomarkers for the diagnosis of gastric carcinoma.World journal of clinical oncology · 2025Article
- Inflammatory factors collaboratively linkFrontiers in immunology · 2025Review
- Sesquiterpene lactones and cancer: new insight into antitumor and anti-inflammatory effects of parthenolide-derived Dimethylaminomicheliolide and Micheliolide.Frontiers in pharmacology · 2025Review
- Celecoxib Combined with Tocilizumab Has Anti-Inflammatory Effects and Promotes the Recovery of Damaged Cartilage via the Nrf2/HO-1 Pathway In Vitro.Biomolecules · 2024Article
- Microfluidic-SERS sensing system based on dual signal amplification and aptamer for gastric cancer detection.Mikrochimica acta · 2024Article
- Targeting interleukin-6 as a treatment approach for peritoneal carcinomatosis.Journal of translational medicine · 2024Review
- Article
- Expression of heterologous heparan sulphate binding protein of3 Biotech · 2023Article
- Role of non-coding RNA in immune microenvironment and anticancer therapy of gastric cancer.Journal of molecular medicine (Berlin, Germany) · 2022Review
- Review
- Sesquiterpene Lactones and Cancer: New Insight into Antitumor and Anti-inflammatory Effects of Parthenolide-Derived Dimethylaminomicheliolide and Micheliolide.Computational and mathematical methods in medicine · 2022Review
- IL-6: The Link Between Inflammation, Immunity and Breast Cancer.Frontiers in oncology · 2022Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interleukin-6 (IL-6) is a pleiotropic cytokine that affects various functions, including tumor development. Although the importance of IL-6 in gastric cancer has been documented in experimental and clinical studies, the mechanism by which IL-6 promotes gastric cancer remains unclear. In this study, we investigated the role of IL-6 in the epithelial-stromal interaction in gastric tumorigenesis. Immunohistochemical analysis of human gastritis, gastric adenoma, and gastric cancer tissues revealed that IL-6 was frequently detected in the stroma. IL-6-positive cells in the stroma showed positive staining for the fibroblast marker α-smooth muscle actin, suggesting that stromal fibroblasts produce IL-6. We compared IL-6 knockout (IL-6(-/-)) mice with wild-type (WT) mice in a model of gastric tumorigenesis induced by the chemical carcinogen N-methyl-N-nitrosourea. The stromal fibroblasts expressed IL-6 in tumors from WT mice. Gastric tumorigenesis was attenuated in IL-6(-/-) mice, compared with WT mice. Impaired tumor development in IL-6(-/-) mice was correlated with the decreased activation of STAT3, a factor associated with gastric cancer cell proliferation. In vitro, when gastric cancer cell line was co-cultured with primary human gastric fibroblast, STAT3-related genes including COX-2 and iNOS were induced in gastric cancer cells and this response was attenuated with neutralizing anti-IL-6 receptor antibody. IL-6 production from fibroblasts was increased when fibroblasts were cultured in the presence of gastric cancer cell-conditioned media. IL-6 production from fibroblasts was suppressed by an interleukin-1 (IL-1) receptor antagonist and siRNA inhibition of IL-1α in the fibroblasts. IL-1α mRNA and protein were increased in fibroblast lysate, suggesting that cell-associated IL-1α in fibroblasts may be involved. Our results suggest the importance of IL-6 mediated stromal-epithelial cell interaction in gastric tumorigenesis.
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