Bombesin was originally isolated from amphibian skin, whereas its mammalian counterpart,
gastrin-releasing peptide (GRP), was first identified in the nervous system of the gastrointestinal tract. Whether GRP is present in the human skin is not known.
Bombesin-like
peptides are also known to modulate growth. We therefore investigated whether human
melanoma cell lines express functional GRP-preferring
bombesin receptors 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 of high-affinity binding sites for [125I]-[Tyr4]
bombesin (K(d) 0.31 +/- 0.04 nmol L(-1), 3880 +/- 429 binding sites per cell).
Bombesin dose-dependently increased cytosolic
calcium, but did not alter
interleukin (IL) 1beta-induced reduction of cell viability or
IL-6 secretion, both A375-6-specific cell functions. Growth of A375-6 cells was not altered by
bombesin or the specific GRP receptor antagonist
BIM26226 as measured by [3H]-
thymidine incorporation or
methylene blue assay, whereas
insulin alone or in combination with other potential
growth factors dose-dependently stimulated growth of these cells. The newly characterized GRP-preferring
bombesin receptors on highly malignant human
melanoma cells could initiate studies of growth effects on solid tumours or in vivo scanning using radiolabelled tracers.