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Ultrastructure of ECL cells in Mastomys after long-term treatment with H2 receptor antagonist loxtidine

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Abstract

Gastric ECL-cell hyperplasia and carcinoids (ECLoma) develop after 1 year in rats treated with omeprazole or 2 months in Mastomys treated with loxtidine. The aim of this study was to examine the ultrastructure of ECL cells in Mastomys after loxtidine treatment with an attempt to evaluate whether an impairment of autophagy was involved in the tumorigenesis. Mastomys were given loxtidine for 8 or 27 weeks. Morphological analysis of ECL cells showed that (1) cell size was not increased after 8 or 27 weeks; (2) secretory vesicles, a hallmark feature of welldifferentiated ECL cells, were unchanged after 8 weeks but reduced after 27 weeks; (3) granules were reduced after 8 or 27 weeks; (4) microvesicles were unchanged after the treatment; and (5) vacuoles and lipofuscin bodies were found occasionally after 8 weeks but not at 27 weeks. In addition, the appearance of ECL-cell ultrastructure differed between loxtidine-treated Mastomys and rats treated with omeprazole or subjected to antrectomy, but was similar between Mastomys treated with loxtidine for 27 weeks and mice deficient in CCK2 receptor. We suggest that the ultrastructure of ECL cells in Mastomys after long-term treatment with loxtidine displayed an impaired formation of vacuoles and lipofuscin bodies, markers of the autophagic pathway.

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References

  1. Chen D, Zhao CM, Lindström E, Håkanson R (1999) Rat stomach ECL cells up-date of biology and physiology. Gen Pharmacol 32:413–422

    Article  PubMed  CAS  Google Scholar 

  2. Kidd M, Modlin IM, Tang LH (1998) Gastrin and the enterochromaffin-like cell: an acid update. Dig Surg 15:209–217

    Article  PubMed  CAS  Google Scholar 

  3. Waldum HL, Kleveland PM, Brenna E, Bakke I, Qvigstad G, Martinsen TC, Fossmark R, Gustafsson BI, Sandvik AK (2009) Interactions between gastric acid secretagogues and the localization of the gastrin receptor. Scand J Gastroenterol 44:390–393

    Article  PubMed  CAS  Google Scholar 

  4. Havu N (1986) Enterochromaffin-like cell carcinoids of gastric mucosa in rats after life-long inhibition of gastric secretion. Digestion 35(suppl 1):42–55

    Article  PubMed  Google Scholar 

  5. Modlin IM, Lawton GP, Tang LH, Geibel J, Abraham R, Darr U (1994) The mastomys gastric carcinoid: aspects of enterochromaffin-like cell function. Digestion 55(suppl 3):31–37

    Article  PubMed  Google Scholar 

  6. Håkanson R, Sundler F (1990) Proposed mechanism of induction of gastric carcinoids: the gastrin hypothesis. Eur J Clin Invest 20(suppl 1):S65–S71

    PubMed  Google Scholar 

  7. Waldum HL, Brenna E, Kleveland PM, Sandvik AK (1995) Gastrin-physiological and pathophysiological role: clinical consequences. Dig Dis 13:25–38

    Article  PubMed  CAS  Google Scholar 

  8. Modlin IM, Lye KD, Kidd M (2003) Carcinoid tumors of the stomach. Surg Oncol 12:153–172

    Article  PubMed  Google Scholar 

  9. Waldum HL, Aase S, Kvetnoi I, Brenna E, Sandvik AK, Syversen U, Johnsen G, Vatten L, Polak JM (1998) Neuroendocrine differentiation in human gastric carcinoma. Cancer (Phila) 83:435–444

    Article  CAS  Google Scholar 

  10. Kimura K, Chen D, Lindström E, Yamada H, Zhao CM, Håkanson R (1997) Functional impairment of the individual rat stomach ECL cell in response to sustained hypergastrinemia. Regul Pept 72:69–77

    Article  PubMed  CAS  Google Scholar 

  11. Chen D, Zhao CM, Yamada H, Norlen P, Håkanson R (1998) Novel aspects of gastrin-induced activation of histidine decarboxylase in rat stomach ECL cells. Regul Pept 77:169–175

    Article  PubMed  CAS  Google Scholar 

  12. Zhao CM, Bakke I, Tostrup-Skogaker N, Waldum HL, Håkanson R, Chen D (2001) Functionally impaired, hypertrophic ECL cells accumulate vacuoles and lipofuscin bodies. An ultrastructural study of ECL cells isolated from hypergastrinemic rats. Cell Tissue Res 303:415–422

    Article  PubMed  CAS  Google Scholar 

  13. Håkanson R, Tielemans Y, Chen D, Andersson K, Mattsson H, Sundler F (1993) Time-dependent changes in enterochromaffinlike cell kinetics in stomach of hypergastrinemic rats. Gastroenterology 105:15–21

    PubMed  Google Scholar 

  14. Andersson K, Zhao CM, Chen D, Sundler F, Hakanson R (1996) Effect of alpha-fluoromethylhistidine-evoked histamine depletion on ultrastructure of endocrine cells in acid-producing mucosa of stomach in mouse, rat and hamster. Cell Tissue Res 286:375–384

    Article  PubMed  CAS  Google Scholar 

  15. Nilsson O, Wangberg B, Johansson L, Modlin IM, Ahlman H (1992) Praomys (Mastomys) natalensis: a model for gastric carcinoid formation. Yale J Biol Med 65:741–751; discussion 827–829

    PubMed  CAS  Google Scholar 

  16. Tang LH, Modlin IM, Lawton GP, Kidd M, Chinery R (1996) The role of transforming growth factor alpha in the enterochromaffinlike cell tumor autonomy in an African rodent, Mastomys. Gastroenterology 111:1212–1223

    Article  PubMed  CAS  Google Scholar 

  17. Tang LH, Luque EA, Efstathiou JA, Bortecen KH, Kidd M, Tarasova NI, Modlin IM (1997) Gastrin receptor expression and function during rapid transformation of the enterochromaffin-like cells in an African rodent. Regul Pept 72:9–18

    Article  PubMed  CAS  Google Scholar 

  18. Lauffer JM, Tang LH, Zhang T, Hinoue T, Rahbar S, Odo M, Modlin IM, Kidd M (2001) PACAP mediates the neural proliferative pathway of Mastomys enterochromaffin-like cell transformation. Regul Pept 102:157–164

    Article  PubMed  CAS  Google Scholar 

  19. Kidd M, Hinoue T, Eick G, Lye KD, Mane SM, Wen Y, Modlin IM (2004) Global expression analysis of ECL cells in Mastomys natalensis gastric mucosa identifies alterations in the AP-1 pathway induced by gastrin-mediated transformation. Physiol Genomics 20:131–142

    Article  PubMed  CAS  Google Scholar 

  20. Kidd M, Siddique ZL, Drozdov I, Gustafsson BI, Camp RL, Black JW, Boyce M, Modlin IM (2010) The CCK(2) receptor antagonist, YF476, inhibits Mastomys ECL cell hyperplasia and gastric carcinoid tumor development. Regul Pept 162:52–60

    Article  PubMed  CAS  Google Scholar 

  21. Wängberg B, Nilsson O, Theodorsson E, Modlin IM, Dahlstrom A, Ahlman H (1995) Are enterochromaffinlike cell tumours reversible? An experimental study on gastric carcinoids induced in Mastomys by histamine2-receptor blockade. Regul Pept 56:19–33

    Article  PubMed  Google Scholar 

  22. Kölby L, Wängberg B, Ahlman H, Modlin IM, Nilsson O (1998) Histamine metabolism of gastric carcinoids in Mastomys natalensis. Yale J Biol Med 71:207–215

    PubMed  Google Scholar 

  23. Sundler F, Carlsson E, Hakanson R, Larsson H, Mattsson H (1986) Inhibition of gastric acid secretion by omeprazole and ranitidine. Effects on plasma gastrin and gastric histamine, histidine decarboxylase activity and ECL cell density in normal and antrectomized rats. Scand J Gastroenterol Suppl 118:39–46

    Article  PubMed  CAS  Google Scholar 

  24. Chen D, Zhao CM, Andersson K, Sundler F, Håkanson R (1996) Ultrastructure of enterochromaffin-like cells in rat stomach: effects of alpha-fluoromethylhistidine-evoked histamine depletion and hypergastrinemia. Cell Tissue Res 283:469–478

    Article  PubMed  CAS  Google Scholar 

  25. Zhao CM, Chen D, Lintunen M, Panula P, Håkanson R (1999) Effects of reserpine on ECL-cell ultrastructure and histamine compartmentalization in the rat stomach. Cell Tissue Res 295:131–140

    Article  PubMed  CAS  Google Scholar 

  26. Zhao CM, Chen D, Lintunen M, Panula P, Håkanson R (1999) Secretory organelles in ECL cells of the rat stomach: an immunohistochemical and electron-microscopic study. Cell Tissue Res 298:457–470

    Article  PubMed  CAS  Google Scholar 

  27. Chen D, Zhao CM, Al-Haider W, Hakanson R, Rehfeld JF, Kopin AS (2002) Differentiation of gastric ECL cells is altered in CCK(2) receptor-deficient mice. Gastroenterology 123:577–585

    Article  PubMed  CAS  Google Scholar 

  28. Zhao CM, Chen D, Andersson K, Hakanson R (1998) ECL cells of the rat stomach: development of lipofuscin in response to sustained gastrin stimulation. Cell Tissue Res 291:315–323

    Article  PubMed  CAS  Google Scholar 

  29. Essner E, Novikoff AB (1960) Human hepatocellular pigments and lysosomes. J Ultrastruct Res 3:374–391

    Article  PubMed  CAS  Google Scholar 

  30. Miyawaki H (1965) Histochemistry and electron microscopy of iron-containing granules, lysosomes, and lipofuscin in mouse mammary glands. J Natl Cancer Inst 34:601–623

    PubMed  CAS  Google Scholar 

  31. Brun A, Brunk U (1970) Histochemical indications for lysosomal localization of heavy metals in normal rat brain and liver. J Histochem Cytochem 18:820–827

    Article  PubMed  CAS  Google Scholar 

  32. Terman A, Brunk UT (1998) Lipofuscin: mechanisms of formation and increase with age. APMIS 106:265–276

    Article  PubMed  CAS  Google Scholar 

  33. Martinez-Outschoorn UE, Whitaker-Menezes D, Pavlides S, Chiavarina B, Bonuccelli G, Trimmer C, Tsirigos A, Migneco G, Witkiewicz AK, Balliet R, Mercier I, Wang C, Flomenberg N, Howell A, Lin Z, Caro J, Pestell RG, Sotgia F, Lisanti MP (2010) The autophagic tumor stroma model of cancer or “battery-operated tumor growth”: a simple solution to the autophagy paradox. Cell Cycle 9:4297–4306

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Erling Skjalgssons Gate 1, NO-7006, Trondheim, Norway

    Reidar Alexander Vigen, Duan Chen & Chun-Mei Zhao

  2. Gastrointestinal Surgical Pathobiology Research Group, Yale University School of Medicine, New Haven, CT, USA

    Mark Kidd & Irvin M. Modlin

Authors
  1. Reidar Alexander Vigen
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  2. Mark Kidd
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  3. Irvin M. Modlin
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  4. Duan Chen
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  5. Chun-Mei Zhao
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Correspondence to Chun-Mei Zhao.

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Vigen, R.A., Kidd, M., Modlin, I.M. et al. Ultrastructure of ECL cells in Mastomys after long-term treatment with H2 receptor antagonist loxtidine. Med Mol Morphol 45, 80–85 (2012). https://doi.org/10.1007/s00795-011-0544-5

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