Modulation of ICAM-1 expression by alpha-MSH in human melanoma cells and melanocytes.
Alpha-MSH, a proopiomelanocortin (POMC)-derived peptide, is known to be produced in the pituitary, the skin, and melanoma tumors and to possess many biological effects, mainly on melanocyte pigmentation and growth. Moreover, the melanocyte expresses adhesion molecules, including ICAM-1. The latter has been reported to play a role in melanoma spread and associated metastatic process. We conducted a study in order to evaluate the possible effect of MSH on ICAM-1 expression in human cultured malignant and normal melanocytes. Our data show that alpha-MSH inhibits ICAM-1 expression stimulated by TNF in a concentration-dependent manner, both at the protein and gene expression level. Ninety percent inhibition was obtained with 10 nM MSH, while 50% inhibition was achieved with 1 nM. Endogenous cAMP elevation with forskolin as well as an exogenous cAMP stable analogue (Sp-cAMPS) produced the same inhibitory effect. A screening of malignant melanocytes showed that inhibition of ICAM-1 expression could be achieved only in those cells expressing detectable MSH receptors and seemed to correlate with the number of binding sites. In conclusion, our data strongly suggest alpha-MSH as a potent inhibitor of ICAM-1 expression in malignant melanocytes acting through MSH receptor stimulation and subsequent cAMP increase.
Morandini
R
R
LOCE, Institut J. Bordet-ULB, Faculté de Médecine, Bruxelles, Belgium. rmorand@resulb.ulb.ac.be
Boeynaems
J M
JM
Hedley
S J
SJ
MacNeil
S
S
Ghanem
G
G
D000328:Adult; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D008544:Melanocytes / Q000378:metabolism*; D008545:Melanoma / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D011979:Receptors, Pituitary Hormone / Q000378:metabolism; D013873:Thionucleotides / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000521:alpha-MSH / Q000494:pharmacology*
D012333:RNA, Messenger; D011979:Receptors, Pituitary Hormone; D013873:Thionucleotides; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D005576:Colforsin; C016957:adenosine-3',5'-cyclic phosphorothioate; D000521:alpha-MSH; C029446:MSH receptor; D000242:Cyclic AMP