Interleukin-6 antisense oligonucleotides inhibit the growth of human myeloma cell lines.
IL-6 has been shown to be a plasmacytoma growth factor in mice and is believed to play a key role in the development of human multiple myeloma. We investigated the IL-6 requirements for the growth of two human myeloma cell lines, U 266 and RPMI 8226. These cell lines secreted minute amounts of IL-6 (20 U/ml) and featured IL-6 mRNA. IL-6 receptors were detectable at the surface of malignant cells by immunofluorescence. Antibodies to IL-6 did not alter the proliferation of these myeloma cells. There was a dose-dependent decrease, however, in [3H]-thymidine uptake in the presence of IL-6 antisense (and not sense) oligodeoxynucleotides; in the presence of 20 microM IL-6 antisense, an 80 and 95% inhibition of the proliferation of U 266 and RPMI 8226 cells was observed, respectively. These results provide strong evidence for an IL-6 autocrine proliferation of myeloma cells which may occur via internal interaction between IL-6 and the IL-6 receptor.
Levy
Y
Y
Laboratory of Immunochemistry and Immunopathology, Institut National de la Santé et de la Recherche Médicale U 108, Hôpital Saint-Louis, Paris, France.
Tsapis
A
A
Brouet
J C
JC
D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000209:etiology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D015850:Interleukin-6; D016376:Oligonucleotides, Antisense