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PMID: 1864979 Published · ppublish English Journal Article

Interleukin-6 antisense oligonucleotides inhibit the growth of human myeloma cell lines.

The Journal of clinical investigation ·Vol. 88 ·No. 2 ·1991-08-00 ·Pages 696-9

Levy Y, Tsapis A, Brouet JC

Abstract

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.

MeSH Terms
Base Sequence Cell Division/drug effects Humans Interleukin-6/genetics,physiology Molecular Sequence Data Multiple Myeloma/etiology Oligonucleotides, Antisense/pharmacology Tumor Cells, Cultured
Chemicals
Interleukin-6 Oligonucleotides, Antisense
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Levy 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
Brouet J C
References (25)
25 references, click to expand
  1. Interleukin-6 is the central tumor growth factor in vitro and in vivo in multiple myeloma.
    Eur Cytokine Netw. 1990 Oct-Nov;1(4):193-201 PMID: 2104241
  2. Detection of specific sequences among DNA fragments separated by gel electrophoresis.
    J Mol Biol. 1975 Nov 5;98(3):503-17 PMID: 1195397
  3. Autocrine stimulation of intracellular PDGF receptors in v-sis-transformed cells.
    Science. 1988 Feb 19;239(4842):914-6 PMID: 2829358
  4. Rapid turnover of the platelet-derived growth factor receptor in sis-transformed cells and reversal by suramin. Implications for the mechanism of autocrine transformation.
    J Biol Chem. 1988 Sep 5;263(25):12608-18 PMID: 2842336
  5. The productive gene for alpha-H chain disease protein MAL is highly modified by insertion-deletion processes.
    J Immunol. 1989 Dec 1;143(11):3821-7 PMID: 2555418
  6. The biology of interleukin-6.
    Blood. 1989 Jul;74(1):1-10 PMID: 2473791
  7. Autocrine generation and requirement of BSF-2/IL-6 for human multiple myelomas.
    Nature. 1988 Mar 3;332(6159):83-5 PMID: 3258060
  8. Mechanism of autocrine stimulation in hematopoietic cells producing interleukin-3 after retrovirus-mediated gene transfer.
    Mol Cell Biol. 1989 Jan;9(1):204-13 PMID: 2467186
  9. IgG1 plasmacytosis in interleukin 6 transgenic mice.
    Proc Natl Acad Sci U S A. 1989 Oct;86(19):7547-51 PMID: 2798426
  10. COOH-terminal-modified interleukin-3 is retained intracellularly and stimulates autocrine growth.
    Science. 1989 Sep 29;245(4925):1493-6 PMID: 2789432
  11. Paracrine rather than autocrine regulation of myeloma-cell growth and differentiation by interleukin-6.
    Blood. 1989 Feb;73(2):517-26 PMID: 2783861
  12. Establishment of two interleukin 6 (B cell stimulatory factor 2/interferon beta 2)-dependent human bone marrow-derived myeloma cell lines.
    J Exp Med. 1989 Jan 1;169(1):339-44 PMID: 2783335
  13. Autocrine stimulation after transfer of the granulocyte/macrophage colony-stimulating factor gene and autonomous growth are distinct but interdependent steps in the oncogenic pathway.
    Proc Natl Acad Sci U S A. 1987 Dec;84(23):8458-62 PMID: 3317408
  14. Structure and expression of human B cell stimulatory factor-2 (BSF-2/IL-6) gene.
    EMBO J. 1987 Oct;6(10):2939-45 PMID: 3500852
  15. Identification of the human 26-kD protein, interferon beta 2 (IFN-beta 2), as a B cell hybridoma/plasmacytoma growth factor induced by interleukin 1 and tumor necrosis factor.
    J Exp Med. 1987 Mar 1;165(3):914-9 PMID: 3493322
  16. A macrophage-derived factor required by plasmacytomas for survival and proliferation in vitro.
    Science. 1986 Aug 1;233(4763):566-9 PMID: 3726549
  17. Mouse plasmacytoma growth in vivo: enhancement by interleukin 6 (IL-6) and inhibition by antibodies directed against IL-6 or its receptor.
    J Exp Med. 1990 Sep 1;172(3):997-1000 PMID: 2388041
  18. AIDS Kaposi sarcoma-derived cells produce and respond to interleukin 6.
    Proc Natl Acad Sci U S A. 1990 Jun;87(11):4068-72 PMID: 1693429
  19. Expression of an exogenous interleukin 6 gene in human Epstein Barr virus B cells confers growth advantage and in vivo tumorigenicity.
    J Exp Med. 1990 Jul 1;172(1):61-8 PMID: 2162905
  20. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity.
    Anal Biochem. 1983 Jul 1;132(1):6-13 PMID: 6312838
  21. Primary bioassay of human myeloma stem cells.
    J Clin Invest. 1977 Oct;60(4):846-54 PMID: 302265
  22. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease.
    Biochemistry. 1979 Nov 27;18(24):5294-9 PMID: 518835
  23. A general method for isolation of high molecular weight DNA from eukaryotes.
    Nucleic Acids Res. 1976 Sep;3(9):2303-8 PMID: 987581
  24. Established immunoglobulin producing myeloma (IgE) and lymphoblastoid (IgG) cell lines from an IgE myeloma patient.
    Clin Exp Immunol. 1970 Oct;7(4):477-89 PMID: 4097745
  25. Transformation by v-sis occurs by an internal autoactivation mechanism.
    Science. 1989 Sep 29;245(4925):1496-9 PMID: 2551043
Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
Published
1991-08-00
Pages
696-9
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC295417
Subset
IM
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