Bombesin may stimulate proliferation of human pancreatic cancer cells through an autocrine pathway

International Journal of Cancer. Journal International Du Cancer
Q J WangT E Adrian

Abstract

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 ...Continue Reading

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Citations

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