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High Affinity Binding Sites for Gastrin Releasing Peptide on Human Gastric Cancer and Ménétrier's Mucosa¹

Academic Unit of Surgery [S. R. P., L. F. W., S. J-B., J. N. P.] and Department of Pathology [J. I. W.], St. James's University Hospital, Leeds, LS9 7TF, United Kingdom

The bombesin-like peptides gastrin releasing peptide (GRP) and neuromedin B are found in the submucosal and myenteric plexuses of the human gastrointestinal tract. These peptides are potent mitogens to Swiss 3T3 fibroblasts and are important autocrine growth factors in human small cell lung cancer cells. We have recently described the presence of receptors for the bombesin-like peptide, GRP, on the human gastric cancer cell line St42. In this study, we examined fresh resected gastric cancer and uninvolved mucosa from 23 patients for the presence of binding 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 23 mucosal samples specifically bound bombesin and was the only sample from a patient with Ménétrier's disease, a disorder of mucosal growth known to be premalignant. The early gastric cancer from this patient also possessed high affinity binding sites for GRP. This is the first description of binding sites to bombesin-like peptides on human gastric cancer and Ménétrier's mucosa. The role of bombesin/GRP antagonists in the treatment of gastric cancer warrants investigation.

¹ Supported by Grant L232 from the Yorkshire Cancer Research Campaign, Harrogate, United Kingdom.

² Funded by Glaxo Group Research, Ltd., Greenford, United Kingdom.

³ To whom requests for reprints should be addressed.

⁴ Funded by the Yorkshire Cancer Research Campaign.

Received 8/ 9/93. Accepted 9/17/93.

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