High-affinity binding sites for gastrin-releasing peptide on human colorectal cancer tissue but not uninvolved mucosa

Sr Preston,Lf Woodhouse,Gv Miller,Jn Primrose,S Jones-Blackett

doi:10.1038/bjc.1995.210

Abstract

Human colorectal cancer tissue and matched uninvolved mucosa from 21 patients were examined by radioligand displacement for the presence of binding sites for bombesin-like peptides. Five cancers, but no uninvolved mucosa, expressed high-affinity, low-capacity bombesin binding sites (Kd = 6.53 nM, Bmax = 58.6 fmol mg-1 protein) of the gastrin-releasing peptide (GRP)-preferring subtype (IC50 4.8 nM). Bombesin-like peptides may have a role in the pathogenesis of colorectal cancer, and bombesin receptor antagonists may be of value in the treatment of receptor-positive tumours.

Highlights

S_mary Human colorectal cancer tissue and matched uninvolved mucosa from 21 patients were examined by radioligand displacement for the presence of binding sites for bombesin-like peptides
Bombesin-like peptides may have a role in the pathogenesis of colorectal cancer, and bombesin receptor antagonists may be of value in the treatment of receptor-positive tumours
These data led to the search for mammalian bombesin-like peptides and the resultant discovery of gastrin-releasing peptide (GRP) (McDonald et al, 1979) and neuromedin B (NMB) (Minamino et al, 1983)

Summary

Introduction

Bombesin-like peptides may have a role in the pathogenesis of colorectal cancer, and bombesin receptor antagonists may be of value in the treatment of receptor-positive tumours. Bombesin-like peptides are recognised mitogens potently stimulating the growth of Swiss 3T3 fibroblasts (Rozengurt et al, 1983) and human small-cell lung cancer cell lines (Weber et al, 1985) and may be mitogenic to receptor-bearing cells within the gut. The aim of this present study was to examine colorectal cancer tissue and uninvolved mucosa for bombesin family receptors, and to characterise further any binding sites found

Objectives

Methods

Results