GASTRIN REGULATES GROWTH OF HUMAN PANCREATIC-CANCER IN A TONIC AND AUTOCRINE FASHION

The gastrointestinal peptides gastrin and cholecystokinin (CCK) stimul ate growth of human pancreatic cancer through a CCK-B/gastrin-like rec eptor. In the present study we evaluated whether growth of human pancr eatic cancer is endogenously regulated by gastrin. Immunohistochemical examination of BxPC-3 cells and tumor xenografts revealed specific ga strin immunoreactivity. Gastrin was detected by radioimmunoassay in pa ncreatic cancer cell extracts and in the growth media. With use of rev erse-transcriptase polymerase chain reaction gastrin gene expression w as detected in both cultured BxPC-3 cancer cells and transplanted tumo rs, as well as seven additional human pancreatic cancer cell lines. Gr owth of BxPC-3 human pancreatic cancer cells in serum-free medium was inhibited by the addition of the CCK-B/gastrin receptor antagonist L-3 65,260, and gastrin treatment reversed the inhibitory effect of the an tagonist. A selective gastrin antibody (Ab 2604) also repressed growth of BxPC-3 cells. Gastrin immunoreactivity was detected in fresh human pancreatic cancer specimens but not in normal human pancreatic tissue . These data provide the first evidence that growth of a human pancrea tic cancer is tonically stimulated by the autocrine production of gast rin. Evidence for the ubiquity of this system was provided by the dete ction of gastrin gene expression in multiple human pancreatic cancer c ell lines and detection of gastrin in cell lines and fresh pancreatic tumors.