The effects of bombesin on three human small cell lung carcinoma cell (SCLC) lines (NCI-H69, NCI-H128, and NCI-H345) have been examined and compared to the effects of the peptide on the mouse fibroblast cell line Swiss 3T3, and the rat pituitary tumor cell line GH3W5. While all three SCLC lines expressed messenger RNA encoding pregastrin releasing peptide (GRP), only the NCI-H345 cells expressed detectable membrane receptors for GRP and responded to nanomolar mncentrations of bombesin as shown by '%GRP binding, total inositol phosphate accumulation, and increased clonal growth in soft agarose. These data show that some SCLC lines are insensitive to bombesi and do not express detectable membrane receptors for GRP.
Key wonk growth factor, gastrin rekasiq peptide, GRP receptor, inositd phospbste, clonal growth Bombesin, a tetradecapeptide isolated from frog skin [ 13, exhibits a wide array of biological activities [2]. In particular, it displays mitogenic properties on mouse fibre blasts and human bronchial epithelial cells in vitro [3,4]. This effect of bombesin on fibroblasts is thought to involve binding of bombesin to high-affinity membrane receptors followed by an increase in intracellular phosphatidylinositol (PI) turnover [ 5,6]. Mammalian counterparts of bombesin have been identified and characterized. These bombinlike peptides, fragments of a 27-amineacid-long peptide, gastrin-releasing peptide (GRP), all share with bombesin the same carboxy terminal heptapeptide. This carboxy terminal portion has been shown to be necessary for biological activity of GRP [7-91. Peptides from the GRP family are produced in human small cell lung cancer (SCLC) cells [1&12]. These peptides have been shown to have mitogenic effects on some SCLC cells in culture [13-151. Furthermore, monoclonal antibodies against the carboxy terminus of GRP were found to inhibit the in vitro growth of SCLC cells in culture, and to reduce tumor growth in nude mice implanted with SCLC cells [ 151. From these data, it has been suggested that bombesin-like peptides from the GRP family