Interleukin-21 is a growth and survival factor for human myeloma cells

DOI PDF 被引用文献3件
  • Anne-Tove Brenne
    From the Department of Cancer Research and Molecular Biology and the Section of Hematology, Department of Environmental Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
  • Torstein Baade Ro
    From the Department of Cancer Research and Molecular Biology and the Section of Hematology, Department of Environmental Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
  • Anders Waage
    From the Department of Cancer Research and Molecular Biology and the Section of Hematology, Department of Environmental Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
  • Anders Sundan
    From the Department of Cancer Research and Molecular Biology and the Section of Hematology, Department of Environmental Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
  • Magne Borset
    From the Department of Cancer Research and Molecular Biology and the Section of Hematology, Department of Environmental Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
  • Henrik Hjorth-Hansen
    From the Department of Cancer Research and Molecular Biology and the Section of Hematology, Department of Environmental Medicine, Norwegian University of Science and Technology, Trondheim, Norway.

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<jats:p>Interleukin-21 (IL-21) is a recently cloned cytokine with homology to IL-2, IL-4, and IL-15. In this study we examined the effects of IL-21 on human myeloma cells. We found that IL-21 induced proliferation and inhibited apoptosis of the IL-6–dependent human myeloma cell lines ANBL-6, IH-1, and OH-2. The potency of IL-21 was close to that of IL-6 in the OH-2 cell line. Neutralizing antibodies to IL-6 or the IL-6 receptor transducer chain (gp130) did not affect IL-21–induced DNA synthesis, indicating that IL-21–induced proliferation was not mediated through these proteins. Tumor necrosis factor (TNF), another stimulator of myeloma cell growth, up-regulated the expression level of IL-21 receptor (IL-21R), and combinations of TNF and IL-21 gave synergistic effects on myeloma cell proliferation. Furthermore, 4 of 9 purified samples of primary myeloma cells showed a significant increase in DNA synthesis on stimulation of the cells by IL-21. By Western blot analysis, we demonstrated that the intracellular signaling pathways of IL-21 in myeloma cells involved phosphorylation of Jak1, Stat3, and Erk1/2 (p44/42 mitogen-activated protein kinase). IL-21 is a novel growth and survival factor in multiple myeloma and may represent a target for future therapy.</jats:p>

収録刊行物

  • Blood

    Blood 99 (10), 3756-3762, 2002-05-15

    American Society of Hematology

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