Advertisement

International Journal of Pancreatology

, Volume 25, Issue 3, pp 181–193 | Cite as

One thousand faces of langerhans islets

  • Parviz M. Pour
  • Bruno M. Schmied
Article

Summary

Studies with different strains of Syrian hamsters and Syrian golden hamsters have revealed the remarkable potential of islet cells to undergo orthotopic and heterotopic metaplasia. The most common spontaneous change included the development of hepatocytes in aged and malnourished hamsters. Of the many other alterations that occurred during carcinogenesis, most of the metaplastic changes originated within the islet periphery and progressed inside and outside the islets. The development of ductular structures within islets and their progression either to structures identical to human serous cystadenoma or to highly invasive adenocarcinomas were the most common alterations. The remarkably greater invasive potential of cancer cells arising within the islets contrasted sharply with the slow growth of the tumors developing within ducts (intraductal tumors). Studies in human tissue also showed development of malignant cells within islets, and, in some cases, transition of islet cells to malignant cells was suggested. The overall results, along with recent findings in other studies in cultured human and hamster islets, indicate the enormous potential of islet cells to differentiate and undergo malignant transformation. Whether the metaplastic and malignant cells derive from stem cells embedded within islets or from transdifferentiated islet cells remains to be seen.

Key Words

Islet metaplasia differentiation cancer hamster human 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Neubert K. Bau und entwicklung des menschlichen pankreas.Arch Entwicklungsmech Organ 1927; 111: 29.CrossRefGoogle Scholar
  2. 2.
    Bencosme SA. The histogenesis and cytology of the pancreatic islets in the rabbit.Am J Anat 1955; 96: 103–151.PubMedCrossRefGoogle Scholar
  3. 3.
    Boquist L. Alloxan administration in the Chines hamster. II. Ultrstructural study of degeneration and subsequent regeneration of the pancreatic islet tissue.Virchows Arch B 1968; 1: 169.Google Scholar
  4. 4.
    Lazarus SS, Volk BW.The Pancreas in Human and Experimental Diabetes. Grune & Stratton, New York, 1968.Google Scholar
  5. 5.
    Ferner H. Beiträge zur Histobiologie der Langerhansschen inseln des Menschen mit besonderer berücksichtigung der Silberzellen und ihrer beziehung zum Pankreas-diabetes.Virchows Arch Pathol Anat 1942; 309: 87–136.CrossRefGoogle Scholar
  6. 6.
    Laidlaw GF. Nesidioblastoma, the islet tumor of the pancreas.Am J Pathol 1938; 14: 125–134.PubMedGoogle Scholar
  7. 7.
    Bensley RR. Studies on the pancreas of the guinea pig.Am J Anat 1911; 12:297.CrossRefGoogle Scholar
  8. 8.
    Bloom W, Fawcett DW. inA Text Book for Histology, 9th ed, WB Saunders, Philadelphia, 1968, p. 614.Google Scholar
  9. 9.
    Pour PM. Islet cells as a component of pancreatic ductal neoplasms. I. Experimental study. Ductular cells, including islet cell precursors, and primary progenitor cells of tumors.Am J Pathol 1978; 90: 295–316.PubMedGoogle Scholar
  10. 10.
    Pour PM, Wilson R. Experimental pancreas tumor, inCancer of the Pancreas, Moossa AR (ed.), Williams and Wilkins, Baltimore, London, 1980; pp. 37–158.Google Scholar
  11. 11.
    Pour PM. Histogenesis of exocrine pancreatic cancer in the hamster model.Envirorn Health Perspect 1984; 56: 229–243.CrossRefGoogle Scholar
  12. 12.
    Takahashi M, Pour PM. Spontaneous pancreas alteration in aging Syrian hamsters.J Natl Cancer Inst 1978; 60: 355–364.PubMedGoogle Scholar
  13. 13.
    Egami H, Takiyama Y, Chaney WG, Cano M, Fujii H, Tomioka T, et al. Comparative studies on expression of tumors-associated antigens in humans and induced pancreatic cancer in Syrian hamster.Int J Pancreatol 1990; 7: 91–100.PubMedGoogle Scholar
  14. 14.
    Pour PM, Sayed SE, Wolf GL. Considerations on the incidence of pancreatic cancer.Cancer Lett 1980; 10:151–154.PubMedCrossRefGoogle Scholar
  15. 15.
    Pour PM, Sayed S, Sayed G, Wolf GL. Hyperplastic preneoplastic and neoplastic lesions found in 83 human pancreas.Am J Clin Pathol 1982; 77: 137–152.PubMedGoogle Scholar
  16. 16.
    Tomioka T, Andrén-Sandberg A, Fujii H, Egami H, Takiyama Y, Pour PM. Comparative histopathological findings in the pancreas of cigarette smokers and nonsmokers.Cancer Lett 1990; 55: 121–128.PubMedCrossRefGoogle Scholar
  17. 17.
    Pour PM, Kazakoff K. Stimulation of islet cell proliferation enhances pancreatic ductal carcinogenesis in the hamster model.Am J Pathol 1996; 149: 1017–1025.PubMedGoogle Scholar
  18. 18.
    Pour PM, Kazakoff K, Carlson K. Inhibition of Streptozotocin- induced islet cell tumors and BOP-induced exoge nous pancreatic tumors in Syrian hamsters.Cancer Res 1990; 50: 1634–1639.PubMedGoogle Scholar
  19. 19.
    Kim JH, Ho SB, Montgomery CK, Young SK. Cell lineage markers in human pancreatic cancer.Cancer 1990; 66: 2134–2143.PubMedCrossRefGoogle Scholar
  20. 20.
    Feyrter F. Über die peripheren endokrinen (parakrinen) Drüsen des Menschen. V. Wisenschft, Wilhelm Maudrich, Wien-Düsseldorf, 1953.Google Scholar
  21. 21.
    Arihiro K, Inai K. Malignant islet cell tumor of the pancreas with multiple hormone production and expression of CEA and CA19-9. Report of an autopsy case.Acta Pathol Jpn 1991; 41(2): 150–157.PubMedGoogle Scholar
  22. 22.
    Kniffin WD, Spencer SK, Memoli VA, LeMarbre PJ. Metastatic islet cell amphicrine carcinoma of the pancreas.Cancer 1988:62: 1999–2004.PubMedCrossRefGoogle Scholar
  23. 23.
    Ordóñez NG, Balsaver AM, Mackay B. Mucinous islet cell (amphicrine) carcinoma of the pancreas associated with watery diarrhea and hypokalemia syndrome.Hum Pathol 1988; 19: 12.CrossRefGoogle Scholar
  24. 24.
    Cossel L. Intermediärzellen im pankreas und zelluläre transformation.Zentralbl Allg Pathol Anat 1987; 133:503–516.Google Scholar
  25. 25.
    Scarpelli DG, Rao MS. Differentiation of regenerating pancreatic cells into hepatocytelike cells.Proc Natl Acad Sci USA 1981; 78: 2577–2581.PubMedCrossRefGoogle Scholar
  26. 26.
    Rao MS, Subbarao V, Reddy JK. Induction of hepatocytes in the pancreas of copper-depleted rats following repletion.Cell Diff 1986; 18: 109–117.CrossRefGoogle Scholar
  27. 27.
    Konishi N, Ward JM, Waalkes M. Pancreatic hepatocytes in Fischer and Wistar rats induced by repeated injections of cadmium chloride.Toxicol Appl Pharmacol 1990; 104, 149–156.PubMedCrossRefGoogle Scholar
  28. 28.
    Tsanadis G, Kotoulas O, Lollis D. Hepatocyte-like cells in the pancreatic islets: study of the human fetal pancreas and experimental models.Histol Histopathol 1995; 10: 1–10.PubMedGoogle Scholar
  29. 29.
    Hamperl H. Benign and malignant oncocytoma.Cancer 1962; 15: 1019–1062.PubMedCrossRefGoogle Scholar
  30. 30.
    Munger BL. The ultrastructure of the exocrine pancreas, inThe Pancreas, Cary LC (ed.), CV Mosby, St. Louis, 1973; pp. 17–31.Google Scholar
  31. 31.
    Hamoudi AB, Misugi K, Grosfeld JL, Reiner CB. Papillary epithelial neoplasm of pancreas in a child.Cancer 1970; 26: 1126–1134.PubMedCrossRefGoogle Scholar
  32. 32.
    Cubilla AL, Fitzgerald PJ. Tumors of the exocrine pancreas, inAtlas of Tumor Pathology, 2nd ser., Fascicle 19, Armed Forces Institute of Pathology, Washington, DC, 1984.Google Scholar
  33. 33.
    Priesel A. Über ein ungewöhnliches Gewächs der Bauchspeiseldrüse.Virchows Arch Pathol Anat 1928; 267: 354–362.CrossRefGoogle Scholar
  34. 34.
    Cubilla AL, Fitzgerlad PJ. Surgical pathology of tumors of the exocrine pancreas, inTumors of the Pancreas, Moossa, AB (ed.) Williams & Wilkins, Baltimore, 1980: pp. 159–193.Google Scholar
  35. 35.
    Liu G, Schmied B, Moyer MP, Weide L, Murphy L, Pour PM. Formation of pancreatic exocrine cells from cultured hamster islets. Submitted.Google Scholar
  36. 36.
    Kerr-Conte J, Pattou F, Lecomte M, Xia Y, Boilly B, Prove C, et al. Ductal cystic formation in collagen-embedded adult human islet preparations.Diabetes 1996; 45: 1108–1114.PubMedCrossRefGoogle Scholar
  37. 37.
    Yuan S, Rosenberg L, Paraskevas S, Agapitos D, Duguid WP. Transdifferentiation of human islets to pancreatic ductal cells in collagen matrix culture.Differentiation 1996; 61: 67–75.PubMedCrossRefGoogle Scholar
  38. 38.
    Bouwens L, De Blay E. Islet morphogenesis and stem cell markers in rat pancreas.J Histochem Cytochem 1996; 44: 947–951.PubMedGoogle Scholar
  39. 39.
    Pour PM, Weide L, Liu G, Kazakoff K, Scheetz M, Toshkov I, et al. Experimental evidence for the origin of ductal type adenocarcinoma from the islets ofLangerhans.Am J Pathol 1997; 150:2167–2180.PubMedGoogle Scholar
  40. 40.
    Yamao K, Nakazawa S, Fujimoto M, Yamada M, Milchgrub S, Albores-Saavedra J. Intraductal papillary mucinous tumors, non-invasive and invasive, inAtlas of Exocrine Pancreatic Tumors. Morphology, Biology and Diagnosis with an International Guide for Tumor Classification. Pour P, Konishi Y., Klöppel G, Longnecker DS (eds.), Springer, Verlag, Japan, 1994: pp. 117–154.Google Scholar
  41. 41.
    Warren S.The Pathology of Diabetes Mellitus. Lea & Febigere, Philadelphia, 1938: p. 25.Google Scholar
  42. 42.
    Kimura W, Morikane K, Esaki Y, Chan WC, Pour PM. Histological and biological patterns of microscopic ductal adenocarcinomas detected incidentally at autopsy.Cancer 1998; 82: 1839–1849.PubMedCrossRefGoogle Scholar
  43. 43.
    Kashiwabara K, Nakajima T, Shinkai H, Fukuda T, Oono Y, Kurabayashi Y, et al. A case of malignant duct-islet cell tumor of the pancreas immunohistochemical and cytofluorometric study.Acta Pathol Jpn 1991; 41(8): 636–641.PubMedGoogle Scholar
  44. 44.
    Kodama T, Mori W. Morphological behavior of carcinomas of the pancreas. 2. Argyrophil cells and langerhans islets in the carcinomatous tissues.Acta Pathol Jpn 1983; 33(3): 483–493.PubMedGoogle Scholar
  45. 45.
    Minkus G, Breuer W, Arun S, Kirsch M, Müller, Jueller J, et al. Ductuloendocrine cell proliferation in the pancreas of two young dogs with diabetes mellitus.Vet Pathol 1997; 34:164–167.PubMedCrossRefGoogle Scholar
  46. 46.
    Pour PM, Permert J, Mogaki M, Fujii H, Kazakoff K. Endocrine aspects of exocrine cancer of the pancreas. Their patterns and suggested biological significance.Am J Clin Pathol 1993; 100:223–230.PubMedGoogle Scholar
  47. 47.
    Pour PM, Morohoshi T. Ductal adenocarcinoma, inAtlas of Exocrine Pancreatic Tumors. Morphology, Biology and Diagnosis with an International Guide for Tumor Classification, Springer Verlag, Japan, 1994; pp. 117-154.Google Scholar
  48. 48.
    Reid JD, Yuh S-L. Petrelli M, Jaffe MB. Ductuloinsular tumors of the pancreas.Cancer 1992; 49: 908–915.CrossRefGoogle Scholar
  49. 49.
    Schlosnagle DC, Campbell WG. The papillary and solid neoplasm of the pancreas: A report of two cases with electron microscopy, one containing neurosecretory granules.Cancer 1981; 47(11): 2603–2610.PubMedCrossRefGoogle Scholar
  50. 50.
    Eusebi V, Capella C, Bondi A, Sessa F, Vezzadinia P, Mancini AM. Endocrine-paracrine cells in pancreatic exocrine carcinomas.Histopathology 1981; 5: 599–613.PubMedCrossRefGoogle Scholar
  51. 51.
    Nonomura A, Mizukami Y, Matsubara F, Kono N, Nakanuma Y. Duct-islet cell tumor of the pancreas.Acta Pathol Jpn 1989; 39: 328–335.PubMedGoogle Scholar
  52. 52.
    Callea F, Goddeeris P, Mukunda RB, Geboes K, Bekaert J, Desmet VJ. Presenece of alpha-1-antitrypsin in pancre- atic carcinoma. Report of four cases with hepatic storage of the protease inhibitor.Appl Pathol 1983; 1: 290–300.PubMedGoogle Scholar
  53. 53.
    Tanno S, Obara T, Shudo R, Fujii T, Sugawara K, Nishino N, et al. α-Fetoprotein producing mucin-producing carcinoma of the pancreas. A case report with immunohisto- chemical study and lectin-affinity profile.Dig Dis Sci 1997; 42:2513–2518.PubMedCrossRefGoogle Scholar
  54. 54.
    Gu D, Lee M-S, Krahl T, Sarvetnick N. Transitional cells in the regenerating pancreas.Development 1994; 120: 1873–1881.PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 1999

Authors and Affiliations

  1. 1.The Eppley Institute for Research in Cancer and Allied Diseases and Department of Pathology and MicrobiologyUniversity of Nebraska Medical CenterOmaha
  2. 2.Visceral and Transplantation SurgeryInselspitalBernSwitzerland

Personalised recommendations