CHARACTERIZATION OF INTERLEUKIN-1-ALPHA-INDUCED MELANOMA CELL MOTILITY - INHIBITION BY TYPE-I AND TYPE-II RECEPTOR-BLOCKING MONOCLONAL-ANTIBODIES

Interleukin-1 alpha (IL-1 alpha) induces cell motility in a variety of benign cell types and in some but not all malignant cell lines in vit ro, This study characterizes the IL-1 alpha-induced motility of an agg ressive human melanoma cell line that expresses both type I and type I I IL-1 receptors. We tested the effect of monoclonal antibodies includ ing function-blocking moAbs against the type I and type II IL-1 recept ors on melanoma cell motility to determine which receptor is involved in signal transduction of IL-1 alpha-induced melanoma cell motility. I L-1 alpha significantly increases MM-RU melanoma cell migration in a d ose-dependent manner using modified Boyden chamber assays at concentra tions 10 to 100 times less than concentrations that significantly inhi bit cell growth. Computer-assisted time-lapse image analysis reveals t hat the motility is inhibited in a dose-dependent manner by neutralizi ng antibodies against IL-1 alpha. Function-blocking monoclonal antibod ies against either type I or type II IL-1 receptors show a significant inhibition of cytokine-induced enhanced cell migration, When both the anti-IL-1 receptor antibodies are added together, the motility respon se is completely blocked to control levels, Taken together the data in dicate that the IL-1 alpha-induced motility of MM-RU melanoma cells is mediated through both type and type II IL-1 receptors. The significan t inhibition of motility by neutralizing IL-1 alpha or blocking either one or both of the IL-1 receptors indicates an integration of IL-1-in duced signals in the induction of melanoma cell migration.