Expression and ligand binding of bombesin receptors in pulmonary and intestinal carcinoids

Introduction: Carcinoids are mainly found in the gastrointestinal (65%) and bronchopulmonary tract (25%). These neuroendocrine tumors secrete a wide range of bioactive peptides, including gastrin releasing peptide and neuromedin B, the mammalian analogs of bombesin. The purpose of this study was to investigate the quantity and localization of bombesin receptors in gastrointestinal and pulmonary carcinoids, and to reveal whether bombesin-like peptides (BLP) and their receptors are of any value in distinguishing pulmonary carcinoids from carcinoids of intestinal origin. Methods: Carcinoid tumors with pulmonary (no.=9) or intestinal (no.=15) localizations were analyzed by immunohistochemistry, autoradiography, and radioimmunoassay, to examine the presence of bombesin receptor subtypes and determine BLP levels in these tumors. Results: All 3 bombesin receptor subtypes (GRPR, NM-BR, and BRS-3) were present on pulmonary and intestinal carcinoids by immunohistochemistry. In pulmonary carcinoids, low receptor ligand binding densities together with high and low BLP levels were found. Intestinal carcinoids showed predominantly high receptor ligand binding densities in combination with low BLP levels. Conclusions: The expression of bombesin receptor subtypes is independent from the carcinoid tumor origin, and is therefore not recommended as a distinction marker, although carcinoids of pulmonary and intestinal origin possess different receptor binding affinities for bombesin and dissimilar BLP levels. The combined presence of bombesin and its receptors might suggest the presence of a paracrine or autocrine growth loop in carcinoids.