Identification of functional GRP-preferring bombesin receptors on human melanoma cells.
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.
Pansky
A
A
Department of Research, University Hospital, Basle, Switzerland.
Peng
F
F
Eberhard
M
M
Baselgia
L
L
Siegrist
W
W
Baumann
J B
JB
Eberle
A N
AN
Beglinger
C
C
Hildebrand
P
P
D001839:Bombesin / Q000031:analogs & derivatives / Q000187:drug effects / Q000378:metabolism* / Q000494:pharmacology; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D002470:Cell Survival; D019886:Gastrin-Releasing Peptide; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis; D008545:Melanoma / Q000378:metabolism*; D010446:Peptide Fragments; D010455:Peptides / Q000378:metabolism / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D018004:Receptors, Bombesin / Q000737:chemistry / Q000502:physiology*; D013696:Temperature; D013997:Time Factors; D014407:Tumor Cells, Cultured
C091872:BIM 26226; D007375:Interleukin-1; D015850:Interleukin-6; D010446:Peptide Fragments; D010455:Peptides; D018004:Receptors, Bombesin; D019886:Gastrin-Releasing Peptide; D001839:Bombesin; D002118:Calcium