PMID- 12357369 OWN - NLM STAT- MEDLINE DCOM- 20021024 LR - 20220316 IS - 0887-6924 (Print) IS - 0887-6924 (Linking) VI - 16 IP - 10 DP - 2002 Oct TI - Interleukin 6 induces monocyte chemoattractant protein-1 expression in myeloma cells. PG - 2142-7 AB - 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. FAU - Arendt, B K AU - Arendt BK AD - Department of Immunology, Mayo Graduate and Medical Schools, Mayo Clinic/Foundation, Rochester, MN 55905, USA. FAU - Velazquez-Dones, A AU - Velazquez-Dones A FAU - Tschumper, R C AU - Tschumper RC FAU - Howell, K G AU - Howell KG FAU - Ansell, S M AU - Ansell SM FAU - Witzig, T E AU - Witzig TE FAU - Jelinek, D F AU - Jelinek DF LA - eng GR - CA62228/CA/NCI NIH HHS/United States GR - CA62242/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Leukemia JT - Leukemia JID - 8704895 RN - 0 (Chemokine CCL2) RN - 0 (DNA Primers) RN - 0 (DNA, Complementary) RN - 0 (Interleukin-6) RN - 0 (RNA, Messenger) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) SB - IM MH - Base Sequence MH - Chemokine CCL2/*genetics MH - DNA Primers MH - DNA, Complementary MH - Enzyme Activation MH - Enzyme-Linked Immunosorbent Assay MH - Flow Cytometry MH - Humans MH - Interleukin-6/*physiology MH - Mitogen-Activated Protein Kinases/metabolism MH - Multiple Myeloma/*metabolism MH - Oligonucleotide Array Sequence Analysis MH - RNA, Messenger/genetics MH - Tumor Cells, Cultured EDAT- 2002/10/03 04:00 MHDA- 2002/10/31 04:00 CRDT- 2002/10/03 04:00 PHST- 2002/01/15 00:00 [received] PHST- 2002/06/20 00:00 [accepted] PHST- 2002/10/03 04:00 [pubmed] PHST- 2002/10/31 04:00 [medline] PHST- 2002/10/03 04:00 [entrez] AID - 10.1038/sj.leu.2402714 [doi] PST - ppublish SO - Leukemia. 2002 Oct;16(10):2142-7. doi: 10.1038/sj.leu.2402714.