EFFECT OF GASTRIN-RELEASING PEPTIDE ON THE PANCREATIC TUMOR-CELL LINE(CAPAN)

TheGastrin-releasing peptide (GRP) has previously been shown to be an autocrine growth factor for small cell lung cancer, and our objective in the study presented here was to determine whether GRP has a similar role in pancreatic cancer. Using I-125-GRP, We demonstrated binding t o specific, saturable, high-affinity sites (K-d = 1 nM; B-max = 245 fm ol/mg protein) in membrane preparations from the pancreatic tumor cell line Capan. The receptors were found to be biologically active. In wh ole cells, a GRP analogue bound to these receptors and stimulated rapi d transfer of tritium from the tritiated lipid inositol pool to inosit ol triphosphates. Exogenous GRP addition stimulated incorporation of [ H-3]thymidine into DNA 20-60%. This stimulatory effect was blocked by the addition of a monoclonal antibody that complexed specifically with the receptor-binding portion of the peptide. In addition, the monoclo nal antibody inhibited the growth of Capan cells in an in vitro growth assay without exogenous peptide. Bombesin receptor-specific antagonis ts also inhibited growth in a similar fashion. These data suggest that paracrine production of GRP may be important in pancreatic tumor grow th, or that low-levels of a GRP-like peptide may play an autocrine rol e in this tumor. (C) 1993 Wiley-Liss, Inc.