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Molecular Cancer
Published in: Molecular Cancer 1/2003

Open Access 01-12-2003 | Review

What is the origin of pancreatic adenocarcinoma?

Authors: Parviz M Pour, Krishan K Pandey, Surinder K Batra

Published in: Molecular Cancer | Issue 1/2003

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Abstract

The concept of pancreatic cancer origin is controversial. Acinar, ductal or islet cells have been hypothesized as the cell of origin. The pros and cons of each of these hypotheses are discussed. Based on the world literature and recent observations, pancreatic cells seem to have potential for phenotypical transdifferentiation, i.e ductal-islet, ductal-acinar, acinar-ductal, acinar-islet, islet-acinar and islet-ductal cells. Although the possibility is discussed that cancer may arise from either islet, ductal or acinar cells, the circumstances favoring the islet cells as the tumor cell origin include their greater transdifferentiation potency into both pancreatic and extrapancreatic cells, the presence of a variety of carcinogen-metabolizing enzymes, some of which are present exclusively in islet cells and the growth factor-rich environment of islets.
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Literature
1.
Schmied BM, Liu G, Matsuzaki H, Ulrich A, Hernberg S, Moyer MP, Weide L, Murphy L, Batra SK, Pour PM: Differentiation of islet cells in long-term culture. Pancreas. 2000, 20: 337-47.CrossRefPubMed
2.
Schmied BM, Ulrich A, Matsuzaki H, Ding X, Ricordi C, Weide L, Moyer MP, Batra SK, Adrian TE, Pour PM: Transdifferentiation of human islet cells in a long-term culture. Pancreas. 2001, 23: 157-71.CrossRefPubMed
3.
Schmied BM, Ulrich AB, Matsuzaki H, Ding X, Ricordi C, Moyer MP, Batra SK, Adrian TE, Pour PM: Maintenance of human islets in long term culture. Differentiation. 2000, 66: 173-80.CrossRefPubMed
4.
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.CrossRefPubMed
5.
Kerr-Conte J, Pattou F, Lecomte-Houcke M, Xia Y, Boilly , Proye C, Lefebvre J: Ductal cyst formation in collagen-embedded adult B human islet preparations. A means to the reproduction of nesidioblastosis in vitro. Diabetes. 1996, 45: 1108-14.CrossRefPubMed
6.
Lucas-Clerc C, Massart C, Campion JP, Launois B, Nicol M: Long-term culture of human pancreatic islets in an extracellular matrix: morphological and metabolic effects. Mol Cell Endocrinol. 1993, 94: 9-20.CrossRefPubMed
7.
8.
Kloeppel G: Endokrines Pankreas und Diabetis Mellitus. Spezielle pathologische Anatomie. Edited by: Doerr W, Seifert. 1981, Berlin: Springer Verlag, 523-728.
9.
Alpert S, Hanahan D, Teitelman G: Hybrid insulin genes reveal a developmental lineage for pancreatic endocrine cells and imply a relationship with neurons. Cell. 1988, 53: 295-308.CrossRefPubMed
10.
De Krijger RR, Aanstoot HJ, Kranenburg G, Reinhard M, Visser WJ, Bruining GJ: The midgestational human fetal pancreas contains cells coexpressing islet hormones. Dev Biol. 1992, 153: 368-75.CrossRefPubMed
11.
Pour PM: Islet cells as a component of pancreatic ductal neoplasms. I. Experimental study: ductular cells, including islet cell precursors, as primary progenitor cells of tumors. Am J Pathol. 1978, 90: 295-316.PubMedCentralPubMed
12.
Pour PM: Mechanism of pseudoductular (tubular) formation during pancreatic carcinogenesis in the hamster model. Am J Pathol. 1988, 130: 335-344.PubMedCentralPubMed
13.
Kodoma T: A light and electron microscopic study on the pancreatic ductal system. Acta Pathol Jpn. 1983, 33: 297-321.
14.
Chen J, Baithun SI, Pollock DJ, Berry CL: Argyrophilic and hormone immunoreactive cells in normal and hyperplastic pancreatic ducts and exocrine pancreatic carcinoma. Virchows Arch A Pathol Anat Histolpathol. 1988, 413: 399-405.CrossRef
15.
16.
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.PubMed
17.
Pour PM, Wilson RB: Experimental tumors of the pancreas. In: Tumors of the pancreas. Edited by: Moossa AR. 1980, Baltimore-London, Williams and Wilkins, 37-158.
18.
Ulrich AB, Schmied BM, Standop J, Schneider MB, Lawson TA, Friess H, Andren-Sandberg A, Buechler MW, Pour PM: Differences in the expression of glutathione S-transferases in normal pancreas, chronic pancreatitis, secondary chronic pancreatitis and pancreatic cancer. Pancreas. 2002, 24: 291-297.CrossRefPubMed
19.
Ulrich AB, Standop J, Schmied BM, Schneider MB, Lawson TA, Pour PM: Species Differences in the Distribution of Drug-metabolizing Enzymes in the Pancreas. Toxicol Pathol. 2002, 30: 247-253.CrossRefPubMed
20.
Ulrich AB, Standop J, Schmied BM, Schneider MB, Lawson TA, Pour PM: Expression of drug-metabolizing enzymes in the pancreas of hamster, mouse, and rat, responding differently to pancreatic carcinogenicity of BOP. Pancreatology. 2002, 2: 519-527.CrossRefPubMed
21.
Standop J, Schneider MB, Ulrich A, Chauhan S, Moniaix N, Buechler MW, Batra SK, Pour PM: The pattern of xenobiotic-metabolizing enzymes in the human pancreas. J Toxicol Environ Health. 2002, 65: 1379-1400.CrossRef
22.
Standop J, Ulrich AB, Schneider MB, Buechler MW, Pour MP: Differences in the exptression of xenobiotic metabolizing enzyme between islets derived from the ventral and dorsal anlage of the pancreas. Pancreatology. 2002, 2: 510-518.CrossRefPubMed
23.
Murakami T, Fujita T, Taguchi T, Nonaka Y, Orita K: The blood vascular bed of the human pancreas, with special reference to the insulo-acinar portal system. Scanning electron microscopy of corrosion casts. Arch Histol Cytol. 1992, 55: 381-95.CrossRefPubMed
24.
Murakami T, Hitomi S, Ohtsuka A, Taguchi T, Fujita T: Pancreatic insulo-acinar portal systems in humans, rats, and some other mammals: scanning electron microscopy of vascular casts. Microsc Res Tech. 1997, 37: 478-88.CrossRefPubMed
25.
Lifson N, Kramlinger KG, Mayrand RR, LE J: Blood flow to the rabbit pancreas with special reference to the islets of Langerhans. Gastroenterology. 1980, 79: 466-473.PubMed
26.
Ohtani O, Ushiki T, Kanazawa H, Fujita T: Microcirculation of the pancreas in the rat and rabbit with special reference to the insulo-acinar portal system and emissary vein of the islet. Arch Histol Jpn. 1986, 49: 45-60.CrossRefPubMed
27.
Miyake T, Murakami T, Ohtsuka A: Incomplete vascular casting for a scanning electron microscope study of the microcirculatory patterns in the rat pancreas. Arch Histol Cytol. 1992, 55: 397-406.CrossRefPubMed
28.
Pour PM, Kazakoff K, Carlson K: Inhibition of streptozotocin-induced islet cell tumors and N-nitrosobis(2-oxopropyl)amine-induced pancreatic exocrine tumors in Syrian hamsters by exogenous insulin. Cancer Res. 1990, 50: 1634-1639.PubMed
29.
Bell RH, Pour PM: Pancreatic carcinogenicity of N-nitrosobis(2-oxopropyl)-amine in diabetic and non-diabetic Chinese hamsters. Cancer Lett. 1987, 34: 221-30.CrossRefPubMed
30.
Pour PM, Kazakoff K: Stimulation of islet cell proliferation enhances pancreatic ductal carcinogenesis in the hamster model. Am J Pathol. 1996, 149: 1017-25.PubMedCentralPubMed
31.
Pour PM, Weide L, Liu G, Kazakoff K, Scheetz M, Toshkov I, Ikematsu Y, Fienhold MA, Sanger W: Experimental evidence for the origin of ductal-type adenocarcinoma from the islets of Langerhans. Am J Pathol. 1997, 150: 2167-80.PubMedCentralPubMed
32.
Fienhold MA, Kazakoff K, Pour PM: The effect of streptozotocin and a high-fat diet on BOP-induced tumors in the pancreas and in the submandibular gland of hamsters bearing transplants of homologous islets. Cancer Lett. 1997, 117: 155-60.CrossRefPubMed
33.
Schmied B, Liu G, Moyer MP, Hernberg IS, Sanger W, Batra S, Pour PM: Induction of adenocarcinoma from hamster pancreatic islet cells treated with N-nitrosobis(2-oxopropyl)amine in vitro. Carcinogenesis. 1999, 20: 317-321.CrossRefPubMed
34.
Ikematsu Y, Liu G, Fienhold MA, Cano M, Adrian TE, Hollingsworth MA, Williamson JE, Sanger W, Tomioka T, Pour PM: In vitro pancreatic ductal cell carcinogenesis. Int J Cancer. 1997, 72: 1095-103.CrossRefPubMed
35.
Takahashi T, Moyer MP, Cano M, Wang QJ, Mountjoy CP, Sanger W, Adrian TE, Sugiura H, Katoh H, Pour PM: Differences in molecular biological, biological and growth characteristics between the immortal and malignant hamster pancreatic ductal cells. Carcinogenesis. 1995, 16: 931-939.CrossRefPubMed
36.
Almoguera C, Shibata D, Forrester K, Martin J, Arnheim N, Perucho M: Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell. 1988, 53: 549-54.CrossRefPubMed
37.
Hruban RH, van Mansfeld AD, Offerhaus GJ, van Weering DH, Allison DC, Goodman SN, Kensler TW, Bose KK, Cameron JL, Bos JL: K-ras oncogene activation in adenocarcinoma of the human pancreas. A study of 82 carcinomas using a combination of mutant-enriched polymerase chain reaction analysis and allele-specific oligonucleotide hybridization. Am J Pathol. 1993, 143: 545-54.PubMedCentralPubMed
38.
Muscarella P, Knobloch TJ, Ulrich AB, Casto BC, Moniaux N, Wittel UA, Melvin WS, Pour PM, Song H, Gold B, Batra SK, Weghorst CM: Identification and sequencing of the Syrian Golden hamster (Mesocricetus auratus) p16(INK4a) and p15(INK4b) cDNAs and their homozygous gene deletion in cheek pouch and pancreatic tumor cells. Gene. 2001, 278: 235-243.CrossRefPubMed
39.
Schutte M, Hruban RH, Geradts J, Maynard R, Hilgers W, Rabindran SK, Moskaluk CA, Hahn SA, Schwarte-Waldhoff I, Schmiegel W, Baylin SB, Kern SE, Herman JG: Abrogation of the Rb/p16 tumor-suppressive pathway in virtually all pancreatic carcinomas. Cancer Res. 1997, 57: 3216-3230.
40.
Alison MR, Poulsom R, Forbes S, Wright NA: An introduction to stem cells. J Pathol. 2002, 197: 419-423.CrossRefPubMed
41.
Kimura W, Morikane K, Esaki Y, Chan WC, Pour PM: Histologic and biologic patterns of microscopic pancreatic ductal adenocarcinomas detected incidentally at autopsy. Cancer. 1998, 82: 1839-49.CrossRefPubMed
42.
Pour PM, Schmied BM, Ulrich AB, Friess H, Andren-Sandberg A, Buchler MW: Abnormal differentiation of islet cells in pancreatic cancer. Pancreatology. 2000, 1: 110-116.CrossRef
43.
Schmied BM, Ulrich AB, Matsuzaki H, Li C, Friess H, Buechler MW, Andren-Sandberg A, Adrian TE, Pour PM: Alteration of the Langerhans islet in pancreatic cancer patients. Int J Pancreatol. 2000, 28: 187-197.CrossRefPubMed
44.
Ogrowsky D, Fawcett J, Althoff J, Wilson R, Pour PM: Structure of the pancreas in Syrian hamsters. Acta Anat (Bases). 1980, 107: 121-128.CrossRef
45.
Pour PM, Morohoshi T: Ductal adenocarcinoma. In: Atlas of Exocrine Pancreatic tumors. Morphology, Biology and Diagnosis with an International Guide for Tumor Classification. Edited by: Pour PM, Konoshi Y, Longnecker DE, Kloeppel G. 1994, Springer Verlag, Japan, 117-154.CrossRef
46.
Tezel E, Nagasaka T, Nomoto S, Sugimoto H, Nakao A: Neuroendocrine-like differentiation in patients with pancreatic carcinoma. Cancer. 2000, 89: 2230-2236.CrossRefPubMed
47.
Guengerich FP: Comparisons of catalytic selectivity of cytochrome P450 subfamily enzymes from different species. Chem Biol Interact. 1997, 106: 161-82.CrossRefPubMed
48.
49.
Cubilla AL, Fitzgerald PJ: Morphological lesions associated with human primary invasive nonendocrine pancreas cancer. Cancer Res. 1976, 36: 2690-2698.PubMed
50.
Kozuka S, Sassa R, Taki T, Masamoto K, Nagasawa S, Saga S, Hasegawa K, Takeuchi M: Relation of pancreatic duct hyperplasia to carcinoma. Cancer. 1979, 43: 1418-1428.CrossRefPubMed
51.
Furukawa T, Chiba R, Kobari M, Matsuno S, Nagura H, Takahashi T: Varying grades of epithelial atypia in the pancreatic ducts of humans. Classification based on morphometry and multivariate analysis and correlated with positive reactions of carcinoembryonic antigen. Arch Pathol Lab Med. 1994, 118: 227-234.PubMed
52.
Brockie E, Anand A, Albores-Saavedra J: Progression of atypical ductal hyperplasia/carcinoma in situ of the pancreas to invasive adenocarcinoma. Ann Diagn Pathol. 1998, 2: 286-292.CrossRefPubMed
53.
Brat DJ, Lillemoe KD, Yeo CJ, Warfield PB, Hruban RH: Progression of pancreatic intraductal neoplasias to infiltrating adenocarcinoma of the pancreas. Am J Surg Pathol. 1998, 22: 163-169.CrossRefPubMed
54.
Hruban RH, Goggins M, Parsons J, Kern SE: Progression model for pancreatic cancer. Clin Cancer Res. 2000, 6: 2969-2972.PubMed
55.
Kern S, Hruban R, Hollingsworth MA, Brand R, Adrian TE, Jaffee E, Tempero MA: A white paper: the product of a pancreas cancer think tank. Cancer Res. 2001, 61: 4923-4932.PubMed
56.
Egami H, Takiyama Y, Pour PM: Induction of multifocal pancreatic cancer after inoculation of hamster pancreatic cancer cell into a defined area of homologous pancreas. Cancer Lett. 1990, 50: 53-56.CrossRefPubMed
57.
Kloppel G, Heitz PU: Pancreatic, non-endocrine tumors. In: Pancreatic Pathology. Edited by: Kloeppel G, Heitz PU. 1984, Churchill Livingstone, 89-
58.
Yamano M, Fujii H, Takagaki T, Kadowaki N, Watanabe H, Shirai T: Genetic progression and divergence in pancreatic carcinoma. Am J Pathol. 2000, 156: 2123-2133.PubMedCentralCrossRefPubMed
59.
Hruban RH, van Mansfeld AD, Offerhaus GJ, van Weering DH, Allison DC, Goodman SN, Kensler TW, Bose KK, Cameron JL, Bos JL: K-ras oncogene activation in adenocarcinoma of the human pancreas. A study of 82 carcinomas using a combination of mutant-enriched polymerase chain reaction analysis and allele-specific oligonucleotide hybridization. Am J Pathol. 1993, 143: 545-54.PubMedCentralPubMed
60.
Day JD, DiGiuseppe JA, Yeo C, Lai-Goldman M, Anderson SM, Goodman SN, Kern SE, Hruban RH: Immunohistochemical evaluation of HER-2/neu expression in pancreatic adenocarcinoma and pancreatic intraepithelial neoplasms. Hum Pathol. 1996, 27: 119-24.CrossRefPubMed
61.
Standop J, Pour PM: A stronger and consistent expression of ErbB2 growth factor receptor in pancreatic islets and neuroendocrine cells compared to pancreatic cancer. Neuroendocrinology.
62.
Wilentz RE, Geradts J, Maynard R, Offerhaus GJ, Kang M, Goggins M, Yeo CJ, Kern SE, Hruban RH: Inactivation of the p16 (INK4A) tumor-suppressor gene in pancreatic duct lesions: loss of intranuclear expression. Cancer Res. 1998, 58: 4740-4744.PubMed
63.
Rozenblum E, Schutte M, Goggins M, Hahn SA, Panzer S, Zahurak M, Goodman SN, Sohn TA, Hruban RH, Yeo CJ, Kern SE: Tumor-suppressive pathways in pancreatic carcinoma. Cancer Res. 1997, 57: 1731-174.PubMed
64.
Moskaluk CA, Hruban RH, Kern SE: p16 and K-ras gene mutations in the intraductal precursors of human pancreatic adenocarcinoma. Cancer Res. 1997, 57: 2140-2143.PubMed
65.
Luettges J, Diederich A, MAOMenke H, Vogel I, Kremer B, Kloeppel G: Ductal lesions in patients with chronic pancreatitis show k-ras mutations in a frequency similar to that in the normal pancreas and lack nuclear immunoreactivity for p53. Cancer. 2000, 88: 2495-2504.CrossRef
66.
Goggins M, Hruban RH, Kern SE: BRCA2 is inactivated late in the development of pancreatic intraepithelial neoplasia: evidence and implications. Am J Pathol. 2000, 156: 1767-1771.PubMedCentralCrossRefPubMed
67.
Andrianifahanana M, Moniaux N, Schmied BM, Ringel J, Friess H, Hollingsworth M, Buechler MW, Aubert JP, Batra SK: Mucin (MUC) gene expression in human pancreatic adenocarcinoma and chronic pancreatitits: a potential role of MUC4 as a tumor marker of diagnostic significance. Clin Cancer Res. 2001, 7: 4033-4040.PubMed
68.
Swartz MJ, Batra SK, Varshney GC, Hollingsworth MA, Yeo CJ, Cameron JL, Wilentz RE, Hruban RH, Argani P: MUC4 Expression increases progressively in pancreatic intraepithelial neoplasia (PanIN). Am J Clin Pathol. 2002, 117: 791-796.CrossRefPubMed
69.
Poulsom R, Alison MR, Forbes SJ, Wrigh NA: Adult stem cell plasticity. J Pathol. 2002, 197: 441-456.CrossRefPubMed
70.
Feyrter F: Ueber die peripheren endokrinen (parakrinen) Druesen des Menschen. Wien-Duesseldorf: Wilhelm Maudrich;. 1953
71.
72.
De Lisle RC, Logsdon CD: Pancreatic acinar cells in culture:expression of acinar and ductal antigens in growth-related manner. Eur J Cell Biol. 1990, 51: 64-75.PubMed
73.
Hall PA, Lemoine NR: Rapid acinar to ductal transdifferentiation in cultured human exocrine pancreas. J Pathol. 1992, 166: 97-103.CrossRefPubMed
Metadata
Title
What is the origin of pancreatic adenocarcinoma?
Authors
Parviz M Pour
Krishan K Pandey
Surinder K Batra
Publication date
01-12-2003
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2003
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-2-13

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