EXPERIMENTAL-EVIDENCE FOR THE ORIGIN OF DUCTAL-TYPE ADENOCARCINOMA FROM THE ISLETS OF LANGERHANS

Citation
Pm. Pour et al., EXPERIMENTAL-EVIDENCE FOR THE ORIGIN OF DUCTAL-TYPE ADENOCARCINOMA FROM THE ISLETS OF LANGERHANS, The American journal of pathology, 150(6), 1997, pp. 2167-2180
Citations number
41
Categorie Soggetti
Pathology
ISSN journal
00029440
Volume
150
Issue
6
Year of publication
1997
Pages
2167 - 2180
Database
ISI
SICI code
0002-9440(1997)150:6<2167:EFTOOD>2.0.ZU;2-6
Abstract
To investigate the role of the islets of langerhans in pancreatic carc inogenesis, freshly isolated islets from male Syrian hamsters were tra nsplanted into the right submandibular glands of 50 female hamsters th at were or were not pretreated with streptozotocin. Thyroid gland frag ments, 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 ca rcinogen N-nitrosobis(2-oxopropyl)amine weekly nt a nose of 40 mg/kg o f body weight for 3 weeks, Between 3 and 8 weeks Inter, 18 of 75 (24%) hamsters developed large ductal-type adenocarcinomas in the submandib ular gland region, where islets were transplanted, but none developed tumors in the left submandibular gland, In 3 of 18 hamsters, tumors we re 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 pancre as of hamsters during pancreatic carcinogenesis, The formation of duct ular structures within islets was also demonstrated in vitro, Some tum or cells in the vicinity of these islets were reactive with anti-insul in. Y chromosome message was found by polymerase chain reaction analys is in one of the three tumors examined, Also, like the induced pancrea tic tumors, all three submandibular gland tumors that were examined ha d the mutation of the c-Ki-ras oncogene at codon 12 and all tumors exp ressed blood group A antigen, These and other findings strongly sugges t that some components of islets, most probably stem cells, are the or igin of ductal-type adenocarcinomas in this model.