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Cited by 168Multiple Myeloma Research and TreatmentsCytokine Signaling Pathways and InteractionsLymphoma Diagnosis and Treatment

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

Brenne, Anne-Tove, Baade Ro, Torstein, Waage, Anders, Sundan, Anders, Borset, Magne, Hjorth-Hansen, Henrik·2002·Blood
DOI 10.1182/blood.v99.10.3756
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Abstract

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.

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Metadata

Authors
Brenne, A.-T., Baade Ro, T., Waage, A., Sundan, A., Borset, M., & Hjorth-Hansen, H.
Affiliations
  • Norwegian University of Science and Technology (NO)
  • 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.
ORCID
Venue
Blood
Publisher
American Society of Hematology
Published
2002-05-15
Volume
99
Issue
10
Pages
3756-3762
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
DOI
10.1182/blood.v99.10.3756
OpenAlex
W2108663319
Cited by
168
References
1
Citations by year
2024: 7 · 2023: 4 · 2022: 4 · 2021: 2 · 2020: 3 · 2019: 5 · 2018: 5 · 2017: 6 · 2016: 4 · 2015: 6 · 2014: 9 · 2013: 5 · 2012: 6
FWCI
5.08
Type
journal article
Language
en
Open access
closed
Locations
  • Blood (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
  • Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
Keywords
IL-21, multiple myeloma, myeloma cell proliferation, apoptosis inhibition, IL-21 receptor, TNF-α, interleukin-6, gp130, JAK1, STAT3, ERK1/2, MAPK signaling, cytokine synergy, primary myeloma cells
MeSH terms
Interleukin-21, Aged, Cell Division, Cell Survival, DNA, Neoplasm, Dose-Response Relationship, Drug, Drug Synergism, Female, Growth Substances, Humans, Interleukins, Male, Membrane Glycoproteins, Middle Aged, Multiple Myeloma, RNA, Neoplasm, Tumor Cells, Cultured, Tumor Necrosis Factor-alpha, Signal Transduction, Antigens, CD, Interleukin-6, Apoptosis, Receptors, Interleukin, Cytokine Receptor gp130, Receptors, Interleukin-21, Interleukin-21 Receptor alpha Subunit

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