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

B. K. Arendt, A. Velazquez-Dones, R. C. Tschumper, K. G. Howell, S. M. Ansell, T. E. Witzig, D. F. Jelinek

Research output: Contribution to journalArticle

35 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2142-2147
Number of pages6
JournalLeukemia
Volume16
Issue number10
DOIs
StatePublished - 2002

Keywords

  • Chemokine
  • Interleukin 6
  • Monocyte chemoattractant protein-1
  • Multiple myeloma

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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