Link between exocrine pancreatic cancer and the endocrine pancreas

Background. The histogenesis of pancreatic cancer is still debatable. Ducta l, ductular, and acinar cells all have been declared the tumor progenitor c ells. Our long-term human and experimental studies indicate that pancreatic ductal adenocarcinomas arise within ductal cells and islets. Supporting st udies are presented in this article. Methods. Several human studies and experimental studies on Syrian hamsters conducted within the last 20 years were used in this article. Hamster and h uman islets were established, and their growth and morphologic changes were examined electron microscopically, immunohistochemically, cytogenetically, and molecular biologically. Results. Studies using the hamster pancreatic cancer model showed that most pancreatic adenocarcinomas develop within islets, most probably from stem cells, which are also believed to be the progenitor cells for tumors that d evelop within ducts. Studies in newly established human and hamster islets culture validated the immense potential of islet cells to differentiate and become malignant. The higher susceptibility of islet cells to become malig nant could be related to their high drug-metabolizing enzymes and their hig h proliferation rate. Dietary studies indicate that the promoting effect of a high-fat diet on pancreatic carcinogenesis is unrelated to the energy in take, but rather is related to its effect on islet cell replication. Conclusion. Experimental and human studies during 20 years of research in o ur laboratories point to the importance of pancreatic islets in the develop ment of ductal-type adenocarcinomas. We believe that pancreatic cancer that develops within ducts, but more frequently within islets, derives from pan creatic stem cells that are distributed within the ductal trees and within the islets.