HIGH-AFFINITY BINDING-SITES FOR GASTRIN-RELEASING PEPTIDE ON HUMAN GASTRIC-CANCER AND MENETRIERS MUCOSA

The bombesin-like peptides gastrin releasing peptide (GRP) and neurome din B are found in the submucosal and myenteric plexuses of the human gastrointestinal tract. These peptides are potent mitogens to Swiss 3T 3 fibroblasts and are important autocrine growth factors in human smal l cell lung cancer cells. We have recently described the presence of r eceptors for the bombesin-like peptide, GRP, on the human gastric canc er cell line St42. In this study, we examined fresh resected gastric c ancer and uninvolved mucosa from 23 patients for the presence of bindi ng sites to the bombesin-like peptides. Thirteen of 23 gastric cancers expressed high affinity binding sites for bombesin (mean K(d) = 3.42 nM; mean B(max) = 40.5 pmol/mg protein), of which 12 were subsequently characterized and found to be of the GRP-preferring subtype. One of 2 3 mucosal samples specifically bound bombesin and was the only sample from a patient with Menetrier's disease, a disorder of mucosal growth known to be premalignant. The early gastric cancer from this patient a lso possessed high affinity binding sites for GRP. This is the first d escription of binding sites to bombesin-like peptides on human gastric cancer and Menetrier's mucosa. The role of bombesin/GRP antagonists i n the treatment of gastric cancer warrants investigation.