Gelatinase-A (MMP-2), gelatinase-B (MMP-9) and membrane type matrix metalloproteinase-1 (MT1-MMP) are involved in different aspects of the pathophysiology of malignant gliomas

Forsyth, P A, Wong, H, Laing, T D, Rewcastle, N B, Morris, D G, Muzik, H, Leco, K J, Johnston, R N, Brasher, P M, Sutherland, G and Edwards, D R (1999) Gelatinase-A (MMP-2), gelatinase-B (MMP-9) and membrane type matrix metalloproteinase-1 (MT1-MMP) are involved in different aspects of the pathophysiology of malignant gliomas. British Journal of Cancer, 79 (11-12). pp. 1828-1835. ISSN 0007-0920

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Abstract

Matrix metalloproteinases (MMPs) have been implicated as important factors in gliomas since they may both facilitate invasion into the surrounding brain and participate in neovascularization. We have tested the hypothesis that deregulated expression of gelatinase-A or B, or an activator of gelatinase-A, MT1-MMP, may contribute directly to human gliomas by quantifying the expression of these MMPs in 46 brain tumour specimens and seven control tissues. Quantitative RT-PCR and gelatin zymography showed that gelatinase-A in glioma specimens was higher than in normal tissue; these were significantly elevated in low grade gliomas and remained elevated in GBMs. Gelatinase-B transcript and activity levels were also higher than in normal brain and more strongly correlated with tumour grade. We did not see a close relationship between the levels of expression of MT1-MMP mRNA and amounts of activated gelatinase-A. In situ hybridization localized gelatinase-A and MT1-MMP transcripts to normal neuronal and glia, malignant glioma cells and blood vessels. In contrast, gelatinase-B showed a more restricted pattern of expression; it was strongly expressed in blood vessels at proliferating margins, as well as tumour cells in some cases. These data suggest that gelatinase-A, -B and MT1-MMP are important in the pathophysiology of human gliomas. The primary role of gelatinase-B may lie in remodelling associated with neovascularization, whereas gelatinase-A and MT1-MMP may be involved in both glial invasion and angiogenesis.

Item Type: Article
Uncontrolled Keywords: brain,brain neoplasms,collagenases,electrophoresis, polyacrylamide gel,gelatinases,glioma,humans,in situ hybridization,matrix metalloproteinase 2,matrix metalloproteinase 9,matrix metalloproteinases, membrane-associated,metalloendopeptidases,rna, messenger,reverse transcriptase polymerase chain reaction
Faculty \ School: Faculty of Science > School of Biological Sciences
Depositing User: Pure Connector
Date Deposited: 25 Mar 2015 13:40
Last Modified: 22 Apr 2020 00:02
URI: https://ueaeprints.uea.ac.uk/id/eprint/52953
DOI: 10.1038/sj.bjc.6990291

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