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 vitro. This study characterizes the IL-1 alpha-induced motility of an aggressive human melanoma cell line that expresses both type I and type II IL-1 receptors. We tested the effect of monoclonal antibodies including function-blocking moAbs against the type I and type II IL-1 receptors on melanoma cell motility to determine which receptor is involved in signal transduction of IL-1 alpha-induced melanoma cell motility. IL-1 alpha significantly increases MM-RU melanoma cell migration in a dose-dependent manner using modified Boyden chamber assays at concentrations 10 to 100 times less than concentrations that significantly inhibit cell growth. Computer-assisted time-lapse image analysis reveals that the motility is inhibited in a dose-dependent manner by neutralizing antibodies against IL-1 alpha. Function-blocking monoclonal antibodies 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-response is completely blocked to control levels. Taken together the data indicate that the IL-1 alpha-induced motility of MM-RU melanoma cells is mediated through both type I and type II IL-1 receptors. The significant 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-induced signals in the induction of melanoma cell migration.
Dekker
S K
SK
Department of Dermatology, University of Leiden, The Netherlands.
Vink
J
J
Bruijn
J A
JA
Mihm
M C
MC
Vermeer
B J
BJ
Byers
H R
HR
D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects*; D005434:Flow Cytometry; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008545:Melanoma / Q000378:metabolism*; D017472:Receptors, Interleukin-1 / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D012878:Skin Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D015375:Receptors, Interleukin-2