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. 1992 Nov-Dec;65(6):741–829.

Praomys (Mastomys) natalensis: a model for gastric carcinoid formation.

O Nilsson 1, B Wängberg 1, L Johansson 1, I M Modlin 1, H Ahlman 1
PMCID: PMC2589773  PMID: 1341076

Abstract

The gastric carcinoid tumors of Praomys (Mastomys) natalensis have been reviewed with respect to histogenesis, development, biochemistry, and morphological properties. Multicentric gastric carcinoids frequently develop in the oxyntic mucosa of aging Mastomys. The development of these tumors can be significantly enhanced by drug-induced hypergastrinemia, e.g., histamine2-receptor blockade. Spontaneous and drug-induced gastric carcinoids are endocrine in nature, as evidenced by their argyrophilic staining properties and chromogranin A content. They are also rich in histidine decarboxylase activity and produce large amounts of histamine, although other hormones, such as peptide YY and enteroglucagon, have also been demonstrated in these tumors. Ultrastructurally, gastric carcinoids are composed of tumor cells with typical secretory granules resembling those of enterochromaffin-like (ECL) cells. A close examination of the gastric carcinoids in Mastomys reveals striking similarities with gastric carcinoids developing in humans suffering from chronic atrophic gastritis type A or from the Zollinger-Ellison syndrome in combination with multiple endocrine neoplasia type 1 (MEN-1). Both these conditions are associated with hypergastrinemia and a higher risk for developing multi-centric gastric carcinoids of ECL-cell origin. The Mastomys tumor model therefore appears to be a significant experimental model in which induction and formation of gastric carcinoid tumors can be studied.

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Selected References

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  1. Ahlman H., Dahlström A., Enerbäck L., Granérus G., Nilsson O., Persson S., Tisell L. E. Two cases of gastric carcinoids: diagnostic and therapeutic aspects. World J Surg. 1988 Jun;12(3):356–361. doi: 10.1007/BF01655671. [DOI] [PubMed] [Google Scholar]
  2. Arntzen L., Wadee A. A., Isaäcson M. Immune responses of two Mastomys sibling species to Yersinia pestis. Infect Immun. 1991 Jun;59(6):1966–1971. doi: 10.1128/iai.59.6.1966-1971.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Betton G. R., Dormer C. S., Wells T., Pert P., Price C. A., Buckley P. Gastric ECL-cell hyperplasia and carcinoids in rodents following chronic administration of H2-antagonists SK&F 93479 and oxmetidine and omeprazole. Toxicol Pathol. 1988;16(2):288–298. doi: 10.1177/019262338801600222. [DOI] [PubMed] [Google Scholar]
  4. Bilchik A. J., Nilsson O., Modlin I. M., Sussman J., Zucker K. A., Adrian T. E. H2-receptor blockade induces peptide YY and enteroglucagon-secreting gastric carcinoids in mastomys. Surgery. 1989 Dec;106(6):1119–1027. [PubMed] [Google Scholar]
  5. Bilchik A. J., Nilsson O., Modlin I. M., Zucker K. A., Adrian T. E. Significance of gastric endocrine tumor and age-related gut peptide alterations in Mastomys. Regul Pept. 1990 Feb 4;27(2):195–207. doi: 10.1016/0167-0115(90)90039-y. [DOI] [PubMed] [Google Scholar]
  6. Borch K. Atrophic gastritis and gastric carcinoid tumours. Ann Med. 1989 Aug;21(4):291–297. doi: 10.3109/07853898909149210. [DOI] [PubMed] [Google Scholar]
  7. Borch K., Renvall H., Kullman E., Wilander E. Gastric carcinoid associated with the syndrome of hypergastrinemic atrophic gastritis. A prospective analysis of 11 cases. Am J Surg Pathol. 1987 Jun;11(6):435–444. doi: 10.1097/00000478-198706000-00004. [DOI] [PubMed] [Google Scholar]
  8. Borch K., Renvall H., Liedberg G. Gastric endocrine cell hyperplasia and carcinoid tumors in pernicious anemia. Gastroenterology. 1985 Mar;88(3):638–648. doi: 10.1016/0016-5085(85)90131-3. [DOI] [PubMed] [Google Scholar]
  9. Bordi C., Yu J. Y., Baggi M. T., Davoli C., Pilato F. P., Baruzzi G., Gardini G., Zamboni G., Franzin G., Papotti M. Gastric carcinoids and their precursor lesions. A histologic and immunohistochemical study of 23 cases. Cancer. 1991 Feb 1;67(3):663–672. doi: 10.1002/1097-0142(19910201)67:3<663::aid-cncr2820670323>3.0.co;2-l. [DOI] [PubMed] [Google Scholar]
  10. Brenna E., Håkanson R., Sundler F., Sandvik A. K., Waldum H. L. The effect of omeprazole-induced hypergastrinemia on the oxyntic mucosa of mastomys. Scand J Gastroenterol. 1991 Jun;26(6):667–672. doi: 10.3109/00365529109043642. [DOI] [PubMed] [Google Scholar]
  11. Capella C., Vassallo G., Solcia E. Light and electron microscopic identification of the histamine-storing argyrophil (ECL) cell in murine stomach and of its equivalent in other mammals. Z Zellforsch Mikrosk Anat. 1971;118(1):68–84. doi: 10.1007/BF00331767. [DOI] [PubMed] [Google Scholar]
  12. Carney J. A., Go V. L., Fairbanks V. F., Moore S. B., Alport E. C., Nora F. E. The syndrome of gastric argyrophil carcinoid tumors and nonantral gastric atrophy. Ann Intern Med. 1983 Dec;99(6):761–766. doi: 10.7326/0003-4819-99-6-761. [DOI] [PubMed] [Google Scholar]
  13. Chiba T., Kinoshita Y., Morishita T., Nakata H., Nakamura A., Hosoda S. Receptors for gastrin on gastric carcinoid tumor membrane of Mastomys natalensis. Biochem Biophys Res Commun. 1991 Jun 14;177(2):739–744. doi: 10.1016/0006-291x(91)91850-c. [DOI] [PubMed] [Google Scholar]
  14. Creutzfeldt W., Stöckmann F., Conlon J. M., Fölsch U. R., Bonatz G., Wülfrath M. Effect of short- and long-term feeding of omeprazole on rat gastric endocrine cells. Digestion. 1986;35 (Suppl 1):84–97. doi: 10.1159/000199384. [DOI] [PubMed] [Google Scholar]
  15. Creutzfeldt W. The achlorhydria-carcinoid sequence: role of gastrin. Digestion. 1988;39(2):61–79. doi: 10.1159/000199609. [DOI] [PubMed] [Google Scholar]
  16. Eckhauser F. E., Lloyd R. V., Thompson N. W., Raper S. E., Vinik A. I. Antrectomy for multicentric, argyrophil gastric carcinoids: a preliminary report. Surgery. 1988 Dec;104(6):1046–1053. [PubMed] [Google Scholar]
  17. Ekman L., Hansson E., Havu N., Carlsson E., Lundberg C. Toxicological studies on omeprazole. Scand J Gastroenterol Suppl. 1985;108:53–69. [PubMed] [Google Scholar]
  18. Godwin J. D., 2nd Carcinoid tumors. An analysis of 2,837 cases. Cancer. 1975 Aug;36(2):560–569. doi: 10.1002/1097-0142(197508)36:2<560::aid-cncr2820360235>3.0.co;2-4. [DOI] [PubMed] [Google Scholar]
  19. Harvey R. F., Bradshaw M. J., Davidson C. M., Wilkinson S. P., Davies P. S. Multifocal gastric carcinoid tumours, achlorhydria, and hypergastrinaemia. Lancet. 1985 Apr 27;1(8435):951–954. doi: 10.1016/s0140-6736(85)91727-1. [DOI] [PubMed] [Google Scholar]
  20. Hirschowitz B. I., Griffith J., Pellegrin D., Cummings O. W. Rapid regression of enterochromaffinlike cell gastric carcinoids in pernicious anemia after antrectomy. Gastroenterology. 1992 Apr;102(4 Pt 1):1409–1418. [PubMed] [Google Scholar]
  21. Hosoda S., Nakamura W., Snell K. C., Stewart H. L. Histamine production by transplantable argyrophilic gastric carcinoid of Praomys (Mastomys) natalensis. Science. 1970 Oct 23;170(3956):454–455. doi: 10.1126/science.170.3956.454. [DOI] [PubMed] [Google Scholar]
  22. Hosoda S., Nakamura W., Snell K. C., Stewart H. L. Histidine decarboxylase in the transplantable argyrophilic gastric carcinoid of Praomys (Mastomys) natalensis. Biochem Pharmacol. 1971 Oct;20(10):2671–2674. doi: 10.1016/0006-2952(71)90176-6. [DOI] [PubMed] [Google Scholar]
  23. Hosoda S., Suyama M., Saito T., Kohmura Y., Hosoda R. Novel flushing provoked by volatile anesthetics in Mastomys natalensis bearing a transplantable substrain of gastric carcinoid that predominantly secretes serotonin. J Natl Cancer Inst. 1984 Jun;72(6):1437–1442. [PubMed] [Google Scholar]
  24. Hosoda S., Suzuki K., Sudo K., Yoshida N., Tanaka C. Transplantable argyrophilic gastric carcinoid of Mastomys natalensis secreting both histamine and serotonin. J Natl Cancer Inst. 1979 Dec;63(6):1447–1450. [PubMed] [Google Scholar]
  25. Håkanson R., Böttcher G., Ekblad E., Panula P., Simonsson M., Dohlsten M., Hallberg T., Sundler F. Histamine in endocrine cells in the stomach. A survey of several species using a panel of histamine antibodies. Histochemistry. 1986;86(1):5–17. doi: 10.1007/BF00492340. [DOI] [PubMed] [Google Scholar]
  26. Håkanson R., Larsson L. I., Owman C., Snell K. C., Sundler F. Fluorescence and electron microscopic histochemistry of endocrine-like cells in gastric mucosa and argyrophil tumor of Praomys (Mastomys) natalensis. Analysis of 5-hydroxytryptamine, histamine, Histidine decarboxylase, and aromatic amino acid decarboxylase. Histochemie. 1973 Oct 3;37(1):23–38. doi: 10.1007/BF00306857. [DOI] [PubMed] [Google Scholar]
  27. Håkanson R., Sundler F. Proposed mechanism of induction of gastric carcinoids: the gastrin hypothesis. Eur J Clin Invest. 1990 Oct;20 (Suppl 1):S65–S71. doi: 10.1111/j.1365-2362.1990.tb01780.x. [DOI] [PubMed] [Google Scholar]
  28. Karnes W. E., Jr, Walsh J. H. The gastrin hypothesis. Implications for antisecretory drug selection. J Clin Gastroenterol. 1990;12 (Suppl 2):S7–12. [PubMed] [Google Scholar]
  29. Kern S. E., Yardley J. H., Lazenby A. J., Boitnott J. K., Yang V. W., Bayless T. M., Sitzmann J. V. Reversal by antrectomy of endocrine cell hyperplasia in the gastric body in pernicious anemia: a morphometric study. Mod Pathol. 1990 Sep;3(5):561–566. [PubMed] [Google Scholar]
  30. Kumazawa H., Takagi H., Sudo K., Nakamura W., Hosoda S. Adenocarcinoma and carcinoid developing spontaneously in the stomach of mutant strains of Mastomys natalensis. Virchows Arch A Pathol Anat Histopathol. 1989;416(2):141–151. doi: 10.1007/BF01606319. [DOI] [PubMed] [Google Scholar]
  31. Larsson H., Carlsson E., Mattsson H., Lundell L., Sundler F., Sundell G., Wallmark B., Watanabe T., Håkanson R. Plasma gastrin and gastric enterochromaffinlike cell activation and proliferation. Studies with omeprazole and ranitidine in intact and antrectomized rats. Gastroenterology. 1986 Feb;90(2):391–399. doi: 10.1016/0016-5085(86)90938-8. [DOI] [PubMed] [Google Scholar]
  32. Mattsson H., Havu N., Bräutigam J., Carlsson K., Lundell L., Carlsson E. Partial gastric corpectomy results in hypergastrinemia and development of gastric enterochromaffinlike-cell carcinoids in the rat. Gastroenterology. 1991 Feb;100(2):311–319. doi: 10.1016/0016-5085(91)90197-s. [DOI] [PubMed] [Google Scholar]
  33. Modlin I. M., Zucker K. A., Zdon M. J., Sussman J., Adrian T. E. Characteristics of the spontaneous gastric endocrine tumor of mastomys. J Surg Res. 1988 Mar;44(3):205–215. doi: 10.1016/0022-4804(88)90049-2. [DOI] [PubMed] [Google Scholar]
  34. Nilsson O., Bilchik A. J., Adrian T. E., Modlin I. M. Intra-ocular transplantation of carcinoid tumours from mastomys and humans. J Pathol. 1990 Apr;160(4):347–356. doi: 10.1002/path.1711600412. [DOI] [PubMed] [Google Scholar]
  35. OETTLE A. G. Spontaneous carcinoma of the glandular stomach in Rattus (mastomys) natalensis, an African rodent. Br J Cancer. 1957 Sep;11(3):415–433. doi: 10.1038/bjc.1957.50. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Pearse A. G. The cytochemistry and ultrastructure of polypeptide hormone-producing cells of the APUD series and the embryologic, physiologic and pathologic implications of the concept. J Histochem Cytochem. 1969 May;17(5):303–313. doi: 10.1177/17.5.303. [DOI] [PubMed] [Google Scholar]
  37. Penston J., Wormsley K. G. Achlorhydria: hypergastrinaemia: carcinoids--a flawed hypothesis? Gut. 1987 Apr;28(4):488–505. doi: 10.1136/gut.28.4.488. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Poynter D., Pick C. R., Harcourt R. A., Selway S. A., Ainge G., Harman I. W., Spurling N. W., Fluck P. A., Cook J. L. Association of long lasting unsurmountable histamine H2 blockade and gastric carcinoid tumours in the rat. Gut. 1985 Dec;26(12):1284–1295. doi: 10.1136/gut.26.12.1284. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Randeria J. D. Animal model: carcinoids and adenocarcinoma of the glandular stomach of Praomys (Mastomys) natalensis. Am J Pathol. 1979 Jul;96(1):359–362. [PMC free article] [PubMed] [Google Scholar]
  40. Reubi J. C., Waser B., Horisberger U., Halter F., Soroka C. J., Kumar R. R., Goldenring J. R., Modlin I. M. Identification of somatostatin and gastrin receptors on enterochromaffin-like cells from Mastomys gastric tumors. Endocrinology. 1992 Jul;131(1):166–172. doi: 10.1210/endo.131.1.1319317. [DOI] [PubMed] [Google Scholar]
  41. Roberts L. J., 2nd, Bloomgarden Z. T., Marney S. R., Jr, Rabin D., Oates J. A. Histamine release from a gastric carcinoid: provocation by pentagastrin and inhibition by somatostatin. Gastroenterology. 1983 Feb;84(2):272–275. [PubMed] [Google Scholar]
  42. Ryberg B., Axelson J., Håkanson R., Sundler F., Mattsson H. Trophic effects of continuous infusion of [Leu15]-gastrin-17 in the rat. Gastroenterology. 1990 Jan;98(1):33–38. doi: 10.1016/0016-5085(90)91287-g. [DOI] [PubMed] [Google Scholar]
  43. Ryberg B., Bishop A. E., Bloom S. R., Carlsson E., Håkanson R., Larsson H., Mattsson H., Polak J. M., Sundler F. Omeprazole and ranitidine, antisecretagogues with different modes of action, are equally effective in causing hyperplasia of enterochromaffin-like cells in rat stomach. Regul Pept. 1989 May;25(2):235–246. doi: 10.1016/0167-0115(89)90265-6. [DOI] [PubMed] [Google Scholar]
  44. Ryberg B., Tielemans Y., Axelson J., Carlsson E., Håkanson R., Mattson H., Sundler F., Willems G. Gastrin stimulates the self-replication rate of enterochromaffinlike cells in the rat stomach. Effects of omeprazole, ranitidine, and gastrin-17 in intact and antrectomized rats. Gastroenterology. 1990 Oct;99(4):935–942. doi: 10.1016/0016-5085(90)90610-d. [DOI] [PubMed] [Google Scholar]
  45. Snell K. C., Stewart H. L. Malignant argyrophilic gastric carcinoids of Praomys (Mastomys) natalensis. Science. 1969 Jan 31;163(3866):470–470. doi: 10.1126/science.163.3866.470. [DOI] [PubMed] [Google Scholar]
  46. Soga J., Koro T., Tazawa K., Kanahara H., Sano M. Argyrophil cell microneoplasia in the Mastomys' stomach--an observation on early carcinoid formation. J Natl Cancer Inst. 1975 Oct;55(4):1001–1006. doi: 10.1093/jnci/55.4.1001. [DOI] [PubMed] [Google Scholar]
  47. Soga J., Tazawa M. D., Ito H. Ultrastructural demonstration of specific secretory granules of Mastomys gastric carcinoids. Acta Med Biol (Niigata) 1969 Sep;17(2):119–124. [PubMed] [Google Scholar]
  48. Solcia E., Bordi C., Creutzfeldt W., Dayal Y., Dayan A. D., Falkmer S., Grimelius L., Havu N. Histopathological classification of nonantral gastric endocrine growths in man. Digestion. 1988;41(4):185–200. doi: 10.1159/000199786. [DOI] [PubMed] [Google Scholar]
  49. Solcia E., Capella C., Fiocca R., Cornaggia M., Bosi F. The gastroenteropancreatic endocrine system and related tumors. Gastroenterol Clin North Am. 1989 Dec;18(4):671–693. [PubMed] [Google Scholar]
  50. Solcia E., Capella C., Fiocca R., Rindi G., Rosai J. Gastric argyrophil carcinoidosis in patients with Zollinger-Ellison syndrome due to type 1 multiple endocrine neoplasia. A newly recognized association. Am J Surg Pathol. 1990 Jun;14(6):503–513. doi: 10.1097/00000478-199006000-00001. [DOI] [PubMed] [Google Scholar]
  51. Solcia E., Capella C., Sessa F., Rindi G., Cornaggia M., Riva C., Villani L. Gastric carcinoids and related endocrine growths. Digestion. 1986;35 (Suppl 1):3–22. doi: 10.1159/000199378. [DOI] [PubMed] [Google Scholar]
  52. Solcia E., Fiocca R., Villani L., Gianatti A., Cornaggia M., Chiaravalli A., Curzio M., Capella C. Morphology and pathogenesis of endocrine hyperplasias, precarcinoid lesions, and carcinoids arising in chronic atrophic gastritis. Scand J Gastroenterol Suppl. 1991;180:146–159. doi: 10.3109/00365529109093193. [DOI] [PubMed] [Google Scholar]
  53. Suyama M., Saito T., Hara K., Kito H., Hosoda S. Production of serotonin by a transplantable strain of histamine-producing primary gastric carcinoid of Mastomys natalensis. J Natl Cancer Inst. 1984 Mar;72(3):751–757. [PubMed] [Google Scholar]
  54. Tielemans Y., Vierendeels T., Willems G. Histochemical and proliferative changes preceding the onset of spontaneous gastric adenocarcinoma in Mastomys natalensis. Virchows Arch A Pathol Anat Histopathol. 1987;411(3):275–281. doi: 10.1007/BF00735034. [DOI] [PubMed] [Google Scholar]
  55. Wormsley K. G. Is hypergastrinaemia dangerous for man? Scand J Gastroenterol Suppl. 1991;180:174–178. doi: 10.3109/00365529109093197. [DOI] [PubMed] [Google Scholar]
  56. Wängberg B., Grimelius L., Granérus G., Conradi N., Jansson S., Ahlman H. The role of gastric resection in the management of multicentric argyrophil gastric carcinoids. Surgery. 1990 Nov;108(5):851–857. [PubMed] [Google Scholar]
  57. Wängberg B., Nilsson O., Theodorsson E., Dahlström A., Ahlman H. The effect of a somatostatin analogue on the release of hormones from human midgut carcinoid tumour cells. Br J Cancer. 1991 Jul;64(1):23–28. doi: 10.1038/bjc.1991.233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Yamada Y., Post S. R., Wang K., Tager H. S., Bell G. I., Seino S. Cloning and functional characterization of a family of human and mouse somatostatin receptors expressed in brain, gastrointestinal tract, and kidney. Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):251–255. doi: 10.1073/pnas.89.1.251. [DOI] [PMC free article] [PubMed] [Google Scholar]

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