ArticleOncotarget2017
Gastrin stimulates a cholecystokinin-2-receptor-expressing cardia progenitor cell and promotes progression of Barrett's-like esophagus.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 2 of them syntheses that pooled it.
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Who cites it
43 citing papers in PubMed, 2 syntheses or guidelines pooled it, 63 citations in OpenAlex.
- Comparative Analysis of Gastroesophageal Reflux Disease Animal Model Methods: A Data Mining of the Past Decade.Digestive diseases and sciences · 2025Pooled it
- Pooled it
- Randomized Controlled Trial of the Gastrin/CCKCancer prevention research (Philadelphia, Pa.) · 2021Trial
- A machine-learning model for staging autoimmune gastritis based on endoscopic and serological features.Frontiers in immunology · 2026Article
- Article
- Article
- Modelling esophageal adenocarcinoma and Barrett's esophagus with patient-derived organoids.Frontiers in molecular biosciences · 2024Review
- Proton pump inhibitors and risk of gastrointestinal cancer: A meta‑analysis of cohort studies.Oncology letters · 2024Article
- Article
- Organoids: Construction and Application in Gastric Cancer.Biomolecules · 2023Review
- Mechanisms and pathophysiology of Barrett oesophagus.Nature reviews. Gastroenterology & hepatology · 2022Review
- Stem Cell Biomarkers and Tumorigenesis in Gastric Cancer.Journal of personalized medicine · 2022Review
- Possible Association between the Use of Proton Pump Inhibitors and HPharmaceuticals (Basel, Switzerland) · 2022Article
- Review
- Chemoprevention of Oesophageal Squamous-Cell Carcinoma and Adenocarcinoma: A Multicentre Retrospective Cohort Study.Digestion · 2022Article
- Investigation of early neoplastic transformation and premalignant biology using genetically engineered organoid models.Computational and structural biotechnology journal · 2022Review
- Gastrin: From Physiology to Gastrointestinal Malignancies.Function (Oxford, England) · 2022Review
- 3D Organoids: An Untapped Platform for Studying Host-Microbiome Interactions in Esophageal Cancers.Microorganisms · 2021Review
- Stem cells and origins of cancer in the upper gastrointestinal tract.Cell stem cell · 2021Review
- Understanding the cellular origin and progression of esophageal cancer using esophageal organoids.Cancer letters · 2021Review
Corrections and comments
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Authors and funding
18 authors at 7 institutions in 4 countries.
Funding
Abstract
objectiveThe incidence of esophageal adenocarcinoma (EAC) is increasing, but factors contributing to malignant progression of its precursor lesion, Barrett's esophagus (BE), have not been defined. Hypergastrinemia caused by long-term use of proton pump inhibitors (PPIs), has been suggested as one possible risk factor. The gastrin receptor, CCK2R, is expressed in the cardia and upregulated in BE, suggesting the involvement of the gastrin-CCK2R pathway in progression. In the L2-IL-1β mouse model, Barrett's-like esophagus arises from the gastric cardia. Therefore, we aimed to analyze the effect of hypergastrinemia on CCK2R+ progenitor cells in L2-IL-1β mice.
designL2-IL-1β mice were mated with hypergastrinemic (INS-GAS) mice or treated with PPIs to examine the effect of hypergastrinemia in BE progression. CCK2R-CreERT crossed with L2-IL-1β mice were used to analyze the lineage progenitor potential of CCK2R+ cells. Cardia glands were cultured in vitro, and the effect of gastrin treatment analyzed. L2-IL-1β mice were treated with a CCK2R antagonist YF476 as a potential chemopreventive drug.
resultsHypergastrinemia resulted in increased proliferation and expansion of Barrett's-like esophagus. Lineage tracing experiments revealed that CCK2R+ cells are long-lived progenitors that can give rise to such lesions under chronic inflammation. Gastrin stimulated organoid growth in cardia culture, while CCK2R inhibition prevented Barrett's-like esophagus and dysplasia.
conclusionsOur data suggest a progression model for BE to EAC in which CCK2R+ progenitor cells, stimulated by hypergastrinemia, proliferate to give rise to metaplasia and dysplasia. Hypergastrinemia can result from PPI use, and the effects of hypergastrinemia in human BE should be studied further.
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Registered trials
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