IDENTIFICATION OF FUNCTIONAL GRP-PREFERRING BOMBESIN RECEPTORS ON HUMAN-MELANOMA CELLS

Bombesin was originally isolated from amphibian skin, wherease its mam malian counterpart, gastrin-releasing peptide (GRP), was first identif ied in the nervous system of the gastrointestinal tract. Whether GRP i s present in the human skin is not known. Bombesin-like peptides are a lso known to modulate growth. We therefore investigated whether human melanoma cell lines express functional GRP-preferring bombesin recepto rs and whether they alter growth or other specific cellular functions of these tumour cells. GRP receptor mRNA was found in HBL, D-10, Me-28 and A375-6 cell lines, but only A375-6 cells express a large number o f high-affinity binding sites for [I-125]-[Tyr(4)] bombesin (K-d 0.31 +/- 0.04 nmol L(-1), 3880 +/- 429 binding sites per cell). Bombesin do se-dependently increased cytosolic calcium, but did not alter interleu kin (IL) Ip-induced reduction of cell viability or IL-6 secretion, bot h A375-6-specific cell functions. Growth of A375-6 cells was not alter ed by bombesin or the specific GRP receptor antagonist BIM26226 as mea sured by [H-3]-thymidine incorporation or methylene blue assay, wherea s insulin alone or in combination with other potential growth factors dose-dependently stimulated growth of these cells. The newly character ized GRP-preferring bombesin receptors on highly malignant human melan oma cells could initiate studies of growth effects on solid tumours or in vivo scanning using radiolabelled tracers.