Insulin-like growth factor-I-induced migration of melanoma cells is mediated by interleukin-8 induction.
Successive events of growth factor-induced autocrine and paracrine activation promote tumor growth and metastasis. Insulin-like growth factor-I (IGF-I) stimulates melanoma cells to grow, survive, and migrate. Interleukin-8 (IL-8) is produced by melanoma cells and has been correlated with melanoma metastasis, but the biological functions of this cytokine have not been elucidated. We show here that IGF-I-induced migration of melanoma cells could be inhibited by neutralizing antibody against IL-8. IGF-I overexpression induced IL-8 production in melanoma cells, especially in biologically early melanomas by accelerating its transcription rate via activation of mitogen-activated protein kinase pathway. IGF-I treatment phosphorylated c-Jun and stimulated the binding of AP-1 but not NF-kappaB to the IL-8 promoter. These data identify IL-8 as a new target of IGF-I in melanoma and suggest that some of the biological functions of IGF-I are mediated by IL-8.
Satyamoorthy
Kapaettu
K
Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
Li
Gang
G
Vaidya
Bhavesh
B
Kalabis
Jiri
J
Herlyn
Meenhard
M
D000911:Antibodies, Monoclonal; D015152:Blotting, Northern; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects*; D002467:Cell Nucleus / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D016209:Interleukin-8 / Q000096:biosynthesis*; D008545:Melanoma / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D017931:DNA Primers; D007328:Insulin; D016209:Interleukin-8; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I