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

被引:43
作者
Arendt, BK
Velazquez-Dones, A
Tschumper, RC
Howell, KG
Ansell, SM
Witzig, TE
Jelinek, DF
机构
[1] Mayo Clin & Mayo Fdn, Mayo Grad Sch, Dept Immunol, Rochester, MN 55905 USA
[2] Mayo Clin & Mayo Fdn, Mayo Med Sch, Dept Immunol, Rochester, MN 55905 USA
[3] Mayo Clin & Mayo Fdn, Mayo Med Sch, Div Hematol, Rochester, MN 55905 USA
[4] Mayo Clin & Mayo Fdn, Mayo Grad Sch, Div Hematol, Rochester, MN 55905 USA
关键词
multiple myeloma; interleukin; 6; chemokine; monocyte chemoattractant protein-1;
D O I
10.1038/sj.leu.2402714
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:2142 / 2147
页数:6
相关论文
共 23 条
[1]   Interleukin-6 induces monocyte chemotactic protein-1 in peripheral blood mononuclear cells and in the U937 cell line [J].
Biswas, P ;
Delfanti, F ;
Bernasconi, S ;
Mengozzi, M ;
Cota, M ;
Polentarutti, N ;
Mantovani, A ;
Lazzarin, A ;
Sozzani, S ;
Poli, G .
BLOOD, 1998, 91 (01) :258-265
[2]  
Charo I F, 1999, Chem Immunol, V72, P30, DOI 10.1159/000058724
[3]  
Choi SJ, 2000, BLOOD, V96, P671
[4]   Identifying intercellular signaling genes expressed in malignant plasma cells by using complementary DNA arrays [J].
De Vos, J ;
Couderc, G ;
Tarte, K ;
Jourdan, M ;
Requirand, G ;
Delteil, MC ;
Rossi, JF ;
Mechti, N ;
Klein, B .
BLOOD, 2001, 98 (03) :771-780
[5]   Immunomagnetic enrichment of CD138 positive cells from weakly infiltrated myeloma patients samples enables the determination of the tumor clone specific IgH rearrangement [J].
Draube, A ;
Pfister, R ;
Vocherodt, M ;
Schuster, S ;
Kube, D ;
Diehl, V ;
Tesch, H .
ANNALS OF HEMATOLOGY, 2001, 80 (02) :83-89
[6]  
Frade JMR, 1997, J IMMUNOL, V159, P5576
[7]   Role of interleukin-6 in the pathogenesis of multiple myeloma [J].
Gadó, K ;
Domján, C ;
Hegyesi, H ;
Falus, A .
CELL BIOLOGY INTERNATIONAL, 2000, 24 (04) :195-209
[8]   Chemokines and disease [J].
Gerard, C ;
Rollins, BJ .
NATURE IMMUNOLOGY, 2001, 2 (02) :108-115
[9]  
Goede V, 1999, INT J CANCER, V82, P765, DOI 10.1002/(SICI)1097-0215(19990827)82:5<765::AID-IJC23>3.0.CO
[10]  
2-F