Interleukin-6 regulation of matrix metalloproteinase (MMP-2 and MMP-9) and tissue inhibitor of metalloproteinase (TIMP-1) expression in malignant non-Hodgkin's lymphomas

被引:188
作者
Kossakowska, AE
Edwards, DR
Prusinkiewicz, C
Zhang, MC
Guo, DL
Urbanski, SJ
Grogan, T
Marquez, LA
Janowska-Wieczorek, A
机构
[1] Univ Calgary, Dept Pathol, Calgary Lab Serv, Calgary, AB, Canada
[2] Univ E Anglia, Sch Biol Sci, Norwich NR4 7TJ, Norfolk, England
[3] Alberta Canc Board, Dept Epidemiol Prevent & Screening, Calgary, AB, Canada
[4] SWOG Lymphoma Lab, Tucson, AZ USA
[5] Univ Alberta, Dept Med, Edmonton, AB, Canada
[6] Univ Alberta, Canadian Blood Serv, Edmonton, AB, Canada
关键词
D O I
10.1182/blood.V94.6.2080.418k30_2080_2089
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We showed previously that human malignant non-Hodgkin's lymphomas (NHL) degrade extracellular matrix (ECM) components through the action of metalloproteinases and that elevated expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) correlated with a poor clinical outcome in patients with NHL. In the present study we sought to investigate whether there is any correlation between the expression of gelatinases (MMP-2 and MMP-9), TIMP-1, and the expression of cytokines and growth factors such as interleukin-1 beta (IL-1 beta), IL-6, IL-10, tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF beta), and basic fibroblast growth factor (bFGF) in human NHL. In lymphoma tissues obtained from 32 patients, elevated expression of IL-6 correlated significantly with elevated messenger RNA (mRNA) levels of MMP-9, MMP-2, and TIMP-1. Moreover, in human lymphoid cell lines of B- and T-cell origin (Raji, Jurkat, and NC-37), IL-6 stimulated production of MMP-9 and MMP-2 but not TIMP-1. In the Matrigel invasion assay IL-6 significantly upregulated transmigration of Raji and Jurkat cells, which in turn was inhibited by recombinant human TIMP-1 and anti-MMP-9 and MMP-2 antibodies. We postulate that IL-6 may play a role in the clinical aggressiveness of human NHL by stimulating MMP production. (C) 1999 by The American Society of Hematology.
引用
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页码:2080 / 2089
页数:10
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