Expression and processing of gastrin in pancreatic adenocarcinoma.
BACKGROUND
Gastrin is a trophic hormone and promotes growth of gastrointestinal and non-gastrointestinal cancers. Studies both in vitro and in vivo have suggested that pancreatic cancer cells not only have the ability to respond to circulating forms of gastrin but also to respond to the autocrine production of gastrin and its precursors. The aim of this study was to identify the expression of CCK-B/gastrin receptor, progastrin, glycine-extended gastrin and amidated gastrin in both normal pancreas and pancreatic adenocarcinoma.


METHODS
Tissue sections from patients with normal pancreas (n = 10) and pancreatic cancer (n = 22) were assessed using immunohistochemical methods for CCK-B/gastrin receptor, progastrin, glycine-extended gastrin and amidated gastrin expression.


RESULTS
Normal pancreas showed no expression of receptor or gastrin isoforms except for occasional cells in the islets. Definite expression of CCK-B/gastrin receptor, progastrin, glycine-extended gastrin and amidated gastrin was observed in 95, 91, 55 and 23 per cent of sections from patients with pancreatic cancer respectively.


CONCLUSIONS
Pancreatic cancer cells express CCK-B/gastrin receptor and gastrin precursor forms in most patients. Expression of the gastrin precursor forms is probably related to autocrine production. New therapeutic strategies need to be developed for the management of pancreatic cancer. Targeting gastrin and its receptor may provide a novel treatment option.
Royal Free and University College Medical School, London and University of Liverpool, Liverpool, UK.
M
M
Caplin
K
K
Savage
K
K
Khan
B
B
Brett
J
J
Rode
A
A
Varro
A
A
Dhillon
D000230:Adenocarcinoma / Q000378:metabolism*; D005755:Gastrins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D009363:Neoplasm Proteins / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D011949:Receptors, Cholecystokinin / Q000378:metabolism
D005755:Gastrins; D009363:Neoplasm Proteins; D011949:Receptors, Cholecystokinin