Bombesin stimulates growth of human gastrinoma

Background. We have previously reported the first establishment and characterization of a functioning human gastrinoma (PT) xenograft. Bombesin, the equivalent of the mammalian gastrin-releasing peptide, has trophic effects on normal and neoplastic tissues of the gastrointestinal tract; the effects of gut hormones on the growth of gastrinoma are not known. The purpose of this study was twofold: (1) to determine the presence of various gut peptides in PT and (2) to determine the effect of bombesin on the growth of PT xenografts. Methods. PT tumors were examined for expression (mRNA and protein) of various gut peptides by Northern hybridization and immunohistochemistry. In addition, PT xenografts were implanted as 3 mm 2 pieces bilaterally subcutaneously in athymic nude mice. Mice were divided into two groups to receive either bombesin (5 μg/kg) or saline administered as intraperitoneal injections every 8 hours. Tumor area was measured twice weekly until mice were sacrificed (day 28), when tumor and normal pancreas were removed, weighed, and assayed for DNA and protein content. Results. Both mRNAs and peptides of gastrin and chromogranin A were present in PT tumors. Bombesin significantly stimulated growth of PT tumors from day 18 until mice were sacrificed (day 28). As expected, bombesin stimulated pancreatic growth. Conclusions. We have demonstrated for the first time that bombesin is a trophic hormone for gastrinoma. The unique cell line PT contains gastrin and chromogranin A and will be a useful model to define the biologic mechanisms controlling the growth of human gastrinomas.