Enterochromaffin-Like (ECL)-Cell Hyperplasia

Enterochromaffin-like (ECL) cell hyperplasia and then irreversible neoplasia can be generated in the African rodent Mastomys natalensis using the H2 receptor blocker, loxtidine, for 8–16 wk. We used a GeneChip approach complemented by standard technologies to identify gene expression alterations in the gastric mucosa during gastrin-mediated ECL cell transformation. Gastric mucosa (mucosal scrapping) and ECL cell-enriched fractions were obtained from untreated Mastomys (controls) and from animals treated with loxtidine for 8 wk (hyperplasia). Tumor ECL cells were obtained by hand-dissection of gastric ECL cell nodules from animals treated with loxtidine for >16 wk and from a spontaneously developed ECL cell tumor. RNA was isolated, examined on rat U34A GeneChips, and comparison analysis was performed to identify altered gene expression. Alterations in gene expressions were examined further by immunohistochemistry, quantitative RT-PCR (Q-RT-PCR), sequencing and Western blot. GeneSpring analysis demonstrated alterations in few genes (<20) in hyperplastic and tumor mucosa. The histamine H1 receptor was consistently increased in proliferating mucosa. This gene change was confirmed by Q-RT-PCR. Other genes showing alterations included neural-(chromogranin A and somatostatin), cell-cycle-, and AP-1-associated genes. Immunostaining confirmed alterations in neural markers. Cluster analysis of ECL cell-enriched samples demonstrated that c- fos and junD were differently regulated. Q-RT-PCR and Western blot in prospectively collected gastric mucosal samples confirmed the differential expression of Fos and Jun. The negative regulators of AP-1, JunD, and Menin were decreased in tumor mucosa. A missense of unknown function was noted in the menin gene. Hypergastrinemia in an animal model of gastric carcinoids differentially altered the histamine type 1 receptor and gene expression and protein composition of AP-1. These results suggest that expression of this receptor and an altered composition of AP-1 with a loss of inhibition play a role in ECL cell transformation.

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Gastric ECL-Cell Hyperplasia and Carcinoids in Rodents Following Chronic Administration of H2-Antagonists SK&F 93479 and Oxmetidine and Omeprazole

Toxicologic Pathology ◽

10.1177/019262338801600222 ◽

1988 ◽

Vol 16 (2) ◽

pp. 288-298 ◽

Cited By ~ 85

Author(s):

Graham R. Betton ◽

Charles S. Dormer ◽

Terry Wells ◽

Pauline Pert ◽

Carolyn A. Price ◽

...

Keyword(s):

Chronic Administration ◽

Cell Hyperplasia ◽

H2 Antagonists ◽

Ecl Cell

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Ablation of parietal cells is associated with ECL-cell hyperplasia in transgenic mice with a genetically engineered ablation of their parietal cell lineage

Gastroenterology ◽

10.1016/s0016-5085(08)81495-3 ◽

2001 ◽

Vol 120 (5) ◽

pp. A301

Author(s):

Duan Chen ◽

Chun-Mei Zhao ◽

Sture Falkmer ◽

Helge L. Waldum ◽

J. Syder ◽

...

Keyword(s):

Transgenic Mice ◽

Parietal Cell ◽

Cell Lineage ◽

Genetically Engineered ◽

Parietal Cells ◽

Cell Hyperplasia ◽

Ecl Cell

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Sa1346 HYPERGASTRINEMIA DUE TO P-CAB (AN EXTREMELY POTENT GASTRIC ACID SECRETION SUPPRESSOR) USE CAUSE SEVERELY PARIETAL CELL PROTRUSION AND ECL CELL HYPERPLASIA.

Gastroenterology ◽

10.1016/s0016-5085(20)31513-4 ◽

2020 ◽

Vol 158 (6) ◽

pp. S-325

Author(s):

Takuji Yamasaki ◽

Yoshihiro Akita ◽

Haruna Miyashita ◽

Ryosuke Miyazaki ◽

Yuki Maruyama ◽

...

Keyword(s):

Acid Secretion ◽

Gastric Acid Secretion ◽

Gastric Acid ◽

Parietal Cell ◽

Cell Hyperplasia ◽

Cell Protrusion ◽

Ecl Cell

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Increased gastric expression of MMP-7 in hypergastrinemia and significance for epithelial-mesenchymal signaling

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00526.2006 ◽

2007 ◽

Vol 292 (4) ◽

pp. G1133-G1140 ◽

Cited By ~ 41

Author(s):

Andrea Varro ◽

Susan Kenny ◽

Elaine Hemers ◽

Catherine McCaig ◽

Sabine Przemeck ◽

...

Keyword(s):

Epithelial Cells ◽

Neutralizing Antibodies ◽

Smooth Muscle Actin ◽

Carcinoid Tumors ◽

Gastric Carcinoid ◽

Gastric Epithelial Cells ◽

Cell Hyperplasia ◽

Gastric Glands ◽

Ecl Cell ◽

Gastric Corpus

Chronic hypergastrinemia is associated with enterochromaffin-like (ECL) cell hyperplasia, which may progress to gastric carcinoid tumors. The latter consists of epithelial cells and stroma, and both compartments usually regress after normalization of hypergastrinemia. We previously showed that matrix metalloproteinase (MMP)-7 in gastric epithelial cells was upregulated by Heliobacter pylori and described MMP-7-dependent reciprocal signaling between the epithelium and a key stromal cell type, the myofibroblast. Here, we describe the regulation of gastric MMP-7 by gastrin and the potential significance for recruiting and maintaining myofibroblast populations. Biopsies of the gastric corpus and ECL cell carcinoid tumors were obtained from hypergastrinemic patients. Western blot analysis, ELISA, immunohistochemistry, and promoter-luciferase (luc) reporter assays were used to study MMP-7 expression. Gastric myofibroblasts were identified by α-smooth muscle actin (α-SMA) expression, and the effects of MMP-7 on myofibroblast proliferation were investigated. In hypergastrinemic patients, there was an increased abundance of MMP-7 and α-SMA in gastric corpus biopsies and ECL cell carcinoid tumors. In the latter, MMP-7 was localized to ECL cells but not stromal cells, which were nevertheless well represented. Gastrin stimulated MMP-7-luc expression in both AGS-GR and primary human gastric epithelial cells. Conditioned medium from gastrin-treated human gastric glands stimulated myofibroblast proliferation, which was inhibited by neutralizing antibodies to MMP-7. MMP-7 increased the proliferation of myofibroblasts via the MAPK and phosphatidylinositol 3-kinase (PI3K) pathways. In conclusion, stimulation of gastric MMP-7 by elevated plasma gastrin may activate epithelial-mesenchymal signaling pathways regulating myofibroblast function via MAPK and PI3K pathways and contribute to stromal deposition in ECL cell carcinoid tumors.

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Chromogranin A: Is It a Useful Marker of Neuroendocrine Tumors?

Journal of Clinical Oncology ◽

10.1200/jco.2006.10.1535 ◽

2007 ◽

Vol 25 (15) ◽

pp. 1967-1973 ◽

Cited By ~ 148

Author(s):

Davide Campana ◽

Francesca Nori ◽

Lidya Piscitelli ◽

Antonio Maria Morselli-Labate ◽

Raffaele Pezzilli ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Plasma Levels ◽

Chromogranin A ◽

Imaging Techniques ◽

High Specificity ◽

Endocrine Tumors ◽

Cell Hyperplasia ◽

Specificity And Sensitivity ◽

Ecl Cell ◽

Number Of Patients

Purpose We evaluated the pattern of chromogranin A (CgA) plasma levels in a large number of patients with neuroendocrine tumors (NETs), in a series of patients with chronic atrophic gastritis (CAG) with and without enterochromaffin-like (ECL) cell hyperplasia, and in healthy participants (HPs). Patients and Methods Two hundred thirty-eight patients with NETs, 42 patients with CAG with or without ECL cell hyperplasia, and 48 HPs were studied. All patients underwent a baseline visit, biochemical routine check-up, imaging techniques, endoscopy, and histologic determination. Results CgA plasma levels were higher in patients with NETs compared with CAG patients or HPs (P < .001). In the NET group, we observed higher CgA levels in patients with diffuse disease compared with patients with local or hepatic disease (P < .001). CgA plasma levels were significantly higher in patients with Zollinger-Ellison syndrome compared with other types of endocrine tumors (P < .001). We found the best cutoff range between HPs and NET patients to be 18 to 19 U/L (sensitivity, 85.3%; specificity, 95.8%). Comparing all participants without neoplasia (HPs, CAG patients, and disease-free patients) and patients with endocrine tumors, the best cutoff range was 31 to 32 U/L (sensitivity, 75.3%; specificity, 84.2%). Setting the specificity at 95%, the cutoff range was 84 to 87 U/L (sensitivity, 55%). Conclusion Our study confirms the high specificity and sensitivity of CgA in diagnosing an endocrine tumor. It is necessary to use a cutoff range of 84 to 87 U/L to obtain a high specificity in diagnosing NETs, with the aim of excluding patients in whom the CgA was elevated as a result of other non-neoplastic diseases.

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