Bombesin stimulates growth of human gastrinoma.

Chung DH, Evers BM, Beauchamp RD, Upp JR, Rajaraman S, Townsend CM, Thompson JC
Surgery. 1992 112 (6): 1059-65

PMID: 1455308

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 mm2 pieces bilaterally subcutaneously in athymic nude mice. Mice were divided into two groups to receive either bombesin (5 micrograms/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.

MeSH Terms (14)

Animals Bombesin Cell Division Chromogranin A Chromogranins Gastrinoma Gastrins Humans Mice Mice, Nude Neoplasm Transplantation RNA, Messenger Transplantation, Heterologous Tumor Cells, Cultured

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