title: Cholecystokinin and pancreatic cancer: the chicken or the egg?
abstract: The gastrointestinal peptide cholecystokinin (CCK) causes the release of pancreatic digestive enzymes and growth of the normal pancreas. Exogenous CCK administration has been used in animal models to study pancreatitis and also as a promoter of carcinogen-induced or Kras-driven pancreatic cancer. Defining CCK receptors in normal human pancreas has been problematic because of its retroperitoneal location, high concentrations of pancreatic proteases, and endogenous RNase. Most studies indicate that the predominant receptor in human pancreas is the CCK-B type, and CCK-A is the predominant form in rodent pancreas. In pancreatic cancer cells and tumors, the role of CCK is better established because receptors are often overexpressed by these cancer cells and stimulation of such receptors promotes growth. Furthermore, in established cancer, endogenous production of CCK and/or gastrin occurs and their actions stimulate the synthesis of more receptors plus growth by an autocrine mechanism. Initially it was thought that the mechanism by which CCK served to potentiate carcinogenesis was by interplay with inflammation in the pancreatic microenvironment. But with the recent findings of CCK receptors on early PanIN (pancreatic intraepithelial neoplasia) lesions and on stellate cells, the question has been raised that perhaps CCK actions are not the result of cancer but an early driving promoter of cancer. This review will summarize what is known regarding CCK, its receptors, and pancreatic cancer, and also what is unknown and requires further investigation to determine which comes first, the chicken or the egg, "CCK or the cancer."
authors.affiliation: 6707 Democracy Blvd., Rm. 655, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892. jsmith2@psu.edu.
authors.forename: Jill P
authors.initials: JP
authors.lastname: Smith
authors.forename: Travis E
authors.initials: TE
authors.lastname: Solomon
mesh_terms: D000818:Animals; D002766:Cholecystokinin / Q000235:genetics* / Q000502:physiology; D018450:Disease Progression; D006801:Humans; D051379:Mice; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D051381:Rats; D011949:Receptors, Cholecystokinin / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D011949:Receptors, Cholecystokinin; D002766:Cholecystokinin
keywords: G protein-coupled; cancer; cholecystokinin; gastrin; pancreas; receptor