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

Kossakowska, Anna E., Edwards, Dylan R., Prusinkiewicz, Christopher, Zhang, Melissa C., Guo, Dianlin, Urbanski, Stefan J., Grogan, Thomas, Marquez, Leah A. and Janowska-Wieczorek, Anna (1999) 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. Blood, 94 (6). pp. 2080-2089. ISSN 0006-4971

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Abstract

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-1β (IL-1β), IL-6, IL-10, tumor necrosis factor α (TNF-α), transforming growth factor β (TGFβ), 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.

Item Type: Article
Faculty \ School: Faculty of Science > School of Biological Sciences
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Depositing User: Pure Connector
Date Deposited: 16 May 2014 11:32
Last Modified: 21 Apr 2020 23:00
URI: https://ueaeprints.uea.ac.uk/id/eprint/48488
DOI:

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