Bombesin may stimulate proliferation of human pancreatic cancer cells through an autocrine pathway.
Bombesin is trophic to normal pancreas and acinar cell adenocarcinoma, but its effects on ductal cell tumors are undetermined. The autocrine growth effects of bombesin on well-differentiated (HPAF, CD11) and poorly differentiated (CD18, PANC-1) human ductal pancreatic cancer cell lines were investigated. Receptor binding of labeled bombesin was measured in a whole-cell microplate assay. Bombesin production was measured by radioimmunoassay. Proliferative responses were quantified using the MTT assay. Messenger RNA for bombesin and its receptor were identified by primer extension analysis. A single class of high-affinity binding sites was detected on HPAF and CD18 cells. Similar affinities and high receptor densities were found on the 2 cell lines. Bombesin was secreted by all 4 cell lines during 24-hr culture in serum-free media, and its recovery was enhanced in the presence of protease inhibitors. Primer extension analysis demonstrated the presence of mRNA for both bombesin and its receptor in HPAF, CD18, CD11 and PANC-1 cells, even though no functional receptor was found in the latter 2 lines. Bombesin significantly stimulated the proliferation of HPAF and CD18 cells. This trophic effect was inhibited by the specific bombesin antagonist RC-3095. Bombesin may act as an autocrine growth factor in some human pancreatic cancer cell lines. Furthermore, other cell lines transcribe mRNA for bombesin receptors but have no functional bombesin receptors, suggesting a genetic or post-translational change in the receptor for these cells. Bombesin may be involved as a growth factor in the development of pancreatic ductal adenocarcinoma in humans. This possible autocrine growth pathway may provide an avenue for therapeutic intervention in this malignant disease.
Wang
Q J
QJ
Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE 68178, USA.
Knezetic
J A
JA
Schally
A V
AV
Pour
P M
PM
Adrian
T E
TE
D001839:Bombesin / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D018004:Receptors, Bombesin / Q000378:metabolism; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D018004:Receptors, Bombesin; D001839:Bombesin