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.