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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-likegrowth 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-{kappa}B 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.