Gastrin-Releasing Peptide Receptors in Normal and Neoplastic Human Uterus: Involvement of Multiple Tissue Compartments

Abstract

Bombesin-like neuropeptides including gastrin-releasing peptide (GRP) and their corresponding receptors, mediate multiple physiological actions and have biological significance in cancer. However, information about the function of these neuropeptides and the incidence, distribution, density, and subtype of their receptors in human uterine tissues is scarce. The objective of the study was to investigate normal and neoplastic human uterine tissues for their bombesin receptor status. In vitro subtype-specific bombesin receptor autoradiography was used in this study. The following tissue samples were taken immediately after surgery: myometrium (n = 41), endometrium (n = 29), leiomyomas (n = 26), leiomyosarcomas (n = 6), endometrial adenocarcinomas (n = 28), and carcinosarcoma (n = 1). Normal uterine tissues expressed GRP receptors (GRP-Rs) in the myometrium, in subsets of secretory endometrial glands, and in subsets of endometrial blood vessels of the late proliferative and the secretory phase. Most leiomyomas (20 of 26) expressed GRP-R but not the leiomyosarcomas. GRP-Rs were also detected in 10 of 28 adenocarcinomas, one of one carcinosarcoma, and in blood vessels surrounding the adenocarcinomas. No other bombesin receptor subtypes (neuromedin B receptors and bb3) were detected. These findings may be of physiological and pathophysiological significance. The expression of GRP-R in glands and vessels during specific phases of the cycle suggests a timely precise physiological action of GRP in these targets; in certain uterine neoplasms, the GRP-R overexpression may contribute to tumor development because GRP is a potent growth factor. Furthermore, these findings may be diagnostically and therapeutically relevant. The expression of GRP-R in leiomyomas may allow distinguishing them from receptor-negative leiomyosarcomas; GRP-R in leiomyomas, in a subset of endometrial adenocarcinomas, carcinosarcomas, and in peritumoral vessels may be candidates for receptor targeting in vivo.