GASTRIN SENSITIVITY OF PRIMARY HUMAN COLORECTAL-CANCER - THE EFFECT OF GASTRIN RECEPTOR ANTAGONISM

The purpose of this study was to determine the effect of the gastrin r eceptor antagonist, CR2093, on basal and gastrin-stimulated growth of primary human colorectal adenocarcinomas and to relate this to gastrin receptor expression. Tumour cells, derived from surgical specimens by enzymatic disaggregation, were grown on matrices of type I collagen a nd irradiated fibroblasts. Gastrin receptor expression was measured by using a mouse monoclonal antibody directed against the gastrin recept or and an avidin-biotin immunocytochemical method. Increased growth in the presence of gastrin-17 (used at physiological concentrations and as assessed by [H-3] thymidine uptake) was shown in 16/34 (47%) tumour s. CR2093 significantly reversed this stimulated growth (P < 0.05, one way analysis of variance) in 9/16 (56.3%) of the tumours and inhibite d the basal growth of 11/34 (32.4%). Basal growth inhibition was rever sed by gastrin-17 in 82% (9/11) of tumours. Gastrin receptor expressio n was widespread, but was not related to the degree of growth response to gastrin, and there was no significant correlation between intensit y of receptor expression and inhibition of basal growth by CR2093. In conclusion, both gastrin-stimulated and basal growth of primary human colorectal can be inhibited by gastrin receptor antagonism, but gastri n receptor expression does not predict the sensitivity of tumours to ( i) the proliferative effects of gastrin or (ii) the inhibitory effects of a gastrin receptor antagonist on basal growth. Antigastrin agents may have clinical value in the treatment of gastrin-sensitive colorect al tumours, and gastrin receptor expression may be related to endogeno us gastrin production by colorectal tumour cells.