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Interleukin 6 induces monocyte chemoattractant protein-1 expression in myeloma cells

Leukemia volume 16, pages 2142–2147 (2002)Cite this article

Abstract

Interleukin 6 (IL-6) is known to play an important role in the biology of the malignant plasma cells in multiple myeloma. In an effort to better understand IL-6 stimulated myeloma cell growth, we have performed gene expression profiling to identify IL-6 early response genes. Using the KAS-6/1 IL-6-dependent human myeloma cell line, IL-6 stimulation dramatically induced expression of monocyte chemoattractant protein-1 (MCP-1) mRNA. To verify this result, we used reverse transcriptase PCR and RNAse protection assays and demonstrated using both assays that MCP-1 is indeed an IL-6 responsive gene in a variety of IL-6-responsive myeloma cell lines. Moreover, we also demonstrated IL-6 stimulated MCP-1 secretion by the myeloma cell lines as well as by fresh patient tumor cells. Lastly, we present evidence that fresh patient tumor cells express mRNA for the MCP-1 receptor, CCR2, as do myeloma cell lines along with a second MCP-1 receptor, CCR11. Although MM cell chemotaxis in response to MCP-1 was only minimal, we were able to demonstrate that MCP-1 stimulated activation of MAPK. Because of the important role that this chemokine plays in both angiogenesis and bone homeostasis, and the ability of MCP-1 to activate myeloma cells, these results suggest a new mechanism by which IL-6 may contribute to disease pathogenesis.

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Acknowledgements

Supported by National Institutes of Health NCI grants CA62242 and CA62228 (DFJ).

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Authors and Affiliations

  1. Department of Immunology, Mayo Graduate and Medical Schools, Mayo Clinic/Foundation, Rochester, MN, USA

    BK Arendt, A Velazquez-Dones, RC Tschumper, KG Howell & DF Jelinek

  2. Division of Hematology, Mayo Graduate and Medical Schools, Mayo Clinic/Foundation, Rochester, MN, USA

    SM Ansell & TE Witzig

Authors
  1. BK Arendt
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  2. A Velazquez-Dones
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  3. RC Tschumper
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  4. KG Howell
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  5. SM Ansell
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  6. TE Witzig
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Arendt, B., Velazquez-Dones, A., Tschumper, R. et al. Interleukin 6 induces monocyte chemoattractant protein-1 expression in myeloma cells. Leukemia 16, 2142–2147 (2002). https://doi.org/10.1038/sj.leu.2402714

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