Experimental evidence for the origin of ductal-type adenocarcinoma from the islets of Langerhans

Parviz M. Pour, Lamont Weide, Guozhen Liu, Katherine Kazakoff, Mark Scheetz, Ilia Toshkov, Yoshito Ikematsu, Margery A. Fienhold, Warren G Sanger

Research output: Contribution to journalArticle

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Abstract

To investigate the role of the islets of Langerhans in pancreatic carcinogenesis, freshly isolated islets from male Syrian hamsters were transplanted into the right submandibular glands of 50 female hamsters that were or were not pre-treated with streptozotocin. Thyroid gland fragments, cellulose powder, and immortal hamster pancreatic ductal cells were injected into the left submandibular gland of the same hamsters. All recipient hamsters were then treated with the potent pancreatic carcinogen N- nitrosobis(2-oxopropyl)amine weekly at a dose of 40 mg/kg of body weight for 3 weeks. Between 3 and 8 weeks later, 18 of 75 (24%) hamsters developed large ductal-type adenocarcinomas in the sub-mandibular gland region, where islets were transplanted, but none developed tumors in the left submandibular gland. In 9 of 18 hamsters, tumors were multiple so that a total of 31 cancers were found. Eleven of these carcinomas were in the vicinity of transplanted islets, eight of which showed intra-insular ductular or cyst formation as seen in the pancreas of hamsters during pancreatic carcinogenesis. The formation of ductular structures within islets was also demonstrated in vitro. Some tumor cells in the vicinity of these islets were reactive with anti-insulin. Y chromosome message was found by polymerase chain reaction analysis in one of the three tumors examined. Also, like the induced pancreatic tumors, all three submandibular gland tumors that were examined bad the mutation of the c-Ki-ras oncogene at codon 12 and all tumors expressed blood group A antigen. These and other findings strongly suggest that some components of islets, most probably stem cells, are the origin of ductal-type adenocarcinomas in this model.

Original languageEnglish (US)
Pages (from-to)2167-2180
Number of pages14
JournalAmerican Journal of Pathology
Volume150
Issue number6
StatePublished - Jun 16 1997

Fingerprint

Islets of Langerhans
Cricetinae
Adenocarcinoma
Submandibular Gland
Neoplasms
nitrosobis(2-oxopropyl)amine
Carcinogenesis
ras Genes
Y Chromosome
Mesocricetus
Streptozocin
Blood Group Antigens
Codon
Cellulose
Carcinogens
Powders
Cysts
Pancreas
Thyroid Gland
Stem Cells

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Pour, P. M., Weide, L., Liu, G., Kazakoff, K., Scheetz, M., Toshkov, I., ... Sanger, W. G. (1997). Experimental evidence for the origin of ductal-type adenocarcinoma from the islets of Langerhans. American Journal of Pathology, 150(6), 2167-2180.

Experimental evidence for the origin of ductal-type adenocarcinoma from the islets of Langerhans. / Pour, Parviz M.; Weide, Lamont; Liu, Guozhen; Kazakoff, Katherine; Scheetz, Mark; Toshkov, Ilia; Ikematsu, Yoshito; Fienhold, Margery A.; Sanger, Warren G.

In: American Journal of Pathology, Vol. 150, No. 6, 16.06.1997, p. 2167-2180.

Research output: Contribution to journalArticle

Pour, PM, Weide, L, Liu, G, Kazakoff, K, Scheetz, M, Toshkov, I, Ikematsu, Y, Fienhold, MA & Sanger, WG 1997, 'Experimental evidence for the origin of ductal-type adenocarcinoma from the islets of Langerhans', American Journal of Pathology, vol. 150, no. 6, pp. 2167-2180.
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 of Langerhans. American Journal of Pathology. 1997 Jun 16;150(6):2167-2180.
Pour, Parviz M. ; Weide, Lamont ; Liu, Guozhen ; Kazakoff, Katherine ; Scheetz, Mark ; Toshkov, Ilia ; Ikematsu, Yoshito ; Fienhold, Margery A. ; Sanger, Warren G. / Experimental evidence for the origin of ductal-type adenocarcinoma from the islets of Langerhans. In: American Journal of Pathology. 1997 ; Vol. 150, No. 6. pp. 2167-2180.
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