Spontaneous ECL-cell carcinomas in cotton rats are prevented by a somatostatin analogue

Martinsen, Tom Christian; Fossmark, Reidar; Waldum, Helge L.

doi:10.1016/s0016-5085(03)81538-x

Cited by 4 publications

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“…We have previously argued that these tumours are of ECL cell origin (Waldum et al 1999, Cui et al 2000, Martinsen et al 2003. The coinciding gastric hypoacidity, hypergastrinaemia and dysplasia of the oxyntic mucosa with a high number of CgA-positive cells strongly suggest an ECL cell origin of these tumours.…”

Section: Discussionmentioning

confidence: 89%

“…Female cotton rats developing hypergastrinaemia have increasing serum gastrin levels from age 2 months. Furthermore, we have found carcinomas in all female cotton rats with hypergastrinaemia lasting more than 4 months and a gastrin receptor antagonist (YF 476) prevents tumour development (Martinsen et al 2003). Hypergastrinaemia induced by partial corpectomy also results in carcinoma in male cotton rats, indicating that gastrin plays a central role in the development of these tumours (R Fossmark et al, unpublished observations).…”

Section: Introductionmentioning

confidence: 83%

“…The coinciding gastric hypoacidity, hypergastrinaemia and dysplasia of the oxyntic mucosa with a high number of CgA-positive cells strongly suggest an ECL cell origin of these tumours. The tumour tissue consists of connective tissue and glandular structures with CgA-and HDCimmunoreactive cells (Martinsen et al 2003), and tumour cells also stain with the Sevier-Munger technique. This present study shows that the spontaneous cancer is prevented by a somatostatin analogue, which supports our previous conclusion that the tumours are ECL cellderived.…”

Section: Discussionmentioning

confidence: 99%

“…This study indicates that the direct anti-proliferative effect of octreotide on the ECL cell is more important than the effect on gastrin producing cells (G-cells) in preventing ECL cell malignancy. Gastric cancer development in hypergastrinaemic cotton rats is also inhibited by a gastrin receptor antagonist (Martinsen et al 2003), indicating that gastrin is essential in the process of carcinogenesis. However, the present study shows that the proliferative effect of gastrin on ECL cells can be inhibited by octreotide, which thus also prevents cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Histologically it is characterized by hyperplasia of ECL cells and dysplasia, often with multiple areas of invasive growth. Cells invading below the muscularis mucosa layer are chromogranin A (CgA)-and histidine decarboxylase (HDC)-immunoreactive and stain positively with the SevierMunger technique (Waldum et al 1999, Cui et al 2000, Martinsen et al 2003. These are strong arguments for an ECL cell origin of the tumours.…”

Section: Introductionmentioning

confidence: 99%

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Spontaneous enterochromaffin-like cell carcinomas in cotton rats (Sigmodon hispidus) are prevented by a somatostatin analogue.

Fossmark

Martinsen²,

Torp³

et al. 2004

Endocr Relat Cancer

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Among inbred female cotton rats (Sigmodon hispidus) 25-50% of the animals develop spontaneous gastric carcinomas; the corresponding figure for male cotton rats is approximately 1%. Animals with carcinomas have hypergastrinaemia and gastric hypo-anacidity and the tumours are derived from enterochromaffin-like (ECL) cells. The mechanism behind the hypo-anacidity is unknown. Carcinomas are found in all female cotton rats with hypergastrinaemia lasting more than 4 months and this represents an excellent animal model for studying gastric carcinogenesis. In this study, the somatostatin analogue octreotide was given to female cotton rats to prevent carcinoma development caused by hypergastrinaemia. Twelve female cotton rats were given monthly injections of long-acting octreotide (5 mg i.m.) for 6 months. A control group of 20 animals was not given injections. Of the 20 control animals, 13 developed hypergastrinaemia and histologically invasive carcinomas or dysplasia. Of the 12 animals in the octreotide group, five developed hypergastrinaemia. None of these five animals developed histological cancer ðP < 0:05Þ; whereas three had dysplasia. However, octreotide did not affect plasma gastrin concentration or antral gastrin mRNA abundance significantly. Dysplasia of the oxyntic mucosa in hypergastrinaemic animals was accompanied by a marked increase in chromogranin A-immunoreactive cells and cells positive for Sevier-Munger staining. The malignant tissue also contained groups of cells with Sevier-Munger staining. In conclusion, octreotide prevented ECL cell carcinomas in hypergastrinaemic cotton rats without lowering the gastrin concentration.

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Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Spontaneous enterochromaffin-like cell carcinomas in cotton rats (Sigmodon hispidus) are prevented by a somatostatin analogue.

Fossmark

Martinsen²,

Torp³

et al. 2004

Endocr Relat Cancer

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Dedifferentiation of enterochromaffin‐like cells in gastric cancer of hypergastrinemic cotton rats

Fossmark

Zhao

Martinsen

et al. 2005

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The role of enterochromaffin‐like (ECL) cells in gastric carcinogenesis is not fully understood. Spontaneous tumours developing in hypergastrinemic female cotton rats have an adenocarcinoma phenotype, but numerous cells in the dysplastic mucosa as well as in the carcinomas are positive for neuroendocrine markers. In the present study of female cotton rats with 2 and 8 months' hypergastrinemia, the oxyntic mucosa of the stomach was examined histologically and immunolabelled for histidine decarboxylase (HDC) and pancreastatin, and hyperplastic and neoplastic ECL cells were evaluated by electron microscopy. These animals developed hyperplasia of the oxyntic mucosa in general and of the ECL cells in particular after 2 months and dysplasia and carcinomas after 8 months. The immunoreactivity of the ECL cells in the oxyntic mucosa was increased at 2 months and declined at 8 months. These histological changes were associated with progressive loss of secretory vesicles and granules in ECL cells. We suggest that ECL cells in hypergastrinemic cotton rats dedifferentiate with time and that the gastric carcinomas may develop from ECL cells.

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ECL-Cell Derived Gastric Cancer in Male Cotton Rats Dosed with the H2-Blocker Loxtidine

et al. 2004

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Spontaneously hypergastrinemic cotton rats (Sigmodon hispidus) develop tumors that have the phenotype of an adenocarcinoma but most likely originate from the enterochromaffin-like (ECL) cells. Among inbred animals ϳ50% of the females, but <1% of males develop spontaneous gastric carcinomas. Gastrin is the principle carcinogen in this model, as >4 months of hypergastrinemia results in carcinoma, but a gastrin receptor antagonist prevents carcinomas. Carcinomas can also be induced by partial corpectomy. In the present study, the insurmountable H2-receptor antagonist loxtidine (200 mg/kg/day) was given to male cotton rats for 6 months. The loxtidine-dosed animals developed hypergastrinemia, whereas control animals remained normogastrinemic. At termination, 4 of 5 cotton rats had cancer located to the oxyntic mucosa, whereas 1 animal had dysplasia. The gastric mucosa of all of the control animals was normal. In the dysplastic mucosa of loxtidine-dosed animals there was a marked increase in chromogranin A-positive cells, where numerous groups of cells also stained positive with the Sevier-Munger technique. In areas of high proliferation and cancer there were also histidine decarboxylase, chromogranin A, and Sevier-Munger-positive cells, altogether indicating an ECL cell origin of the tumors. This represents an interesting animal model where ECL cell-derived gastric cancer can be induced by pharmacological acid inhibition in 6 months.

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Spontaneous ECL-cell carcinomas in cotton rats are prevented by a somatostatin analogue

Cited by 4 publications

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Spontaneous enterochromaffin-like cell carcinomas in cotton rats (Sigmodon hispidus) are prevented by a somatostatin analogue.

Spontaneous enterochromaffin-like cell carcinomas in cotton rats (Sigmodon hispidus) are prevented by a somatostatin analogue.

Dedifferentiation of enterochromaffin‐like cells in gastric cancer of hypergastrinemic cotton rats

ECL-Cell Derived Gastric Cancer in Male Cotton Rats Dosed with the H2-Blocker Loxtidine

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