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
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.