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PMID: 10206300 Published · ppublish English Clinical Trial Comparative Study Controlled Clinical Trial Journal Article Research Support, Non-U.S. Gov't

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 ·Vol. 79 ·No. 11-12 ·1999-04-00 ·Pages 1828-35

Forsyth PA, Wong H, Laing TD, Rewcastle NB, Morris DG, Muzik H, Leco KJ, Johnston RN, Brasher PM, Sutherland G, Edwards DR

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.

MeSH Terms
Brain/metabolism Brain Neoplasms/enzymology,physiopathology Collagenases/genetics,physiology Electrophoresis, Polyacrylamide Gel Gelatinases/genetics,physiology Glioma/enzymology,physiopathology Humans In Situ Hybridization Matrix Metalloproteinase 2 Matrix Metalloproteinase 9 Matrix Metalloproteinases, Membrane-Associated Metalloendopeptidases/genetics,physiology RNA, Messenger/analysis Reverse Transcriptase Polymerase Chain Reaction
Chemicals
RNA, Messenger Collagenases Gelatinases Matrix Metalloproteinases, Membrane-Associated Metalloendopeptidases Matrix Metalloproteinase 2 Matrix Metalloproteinase 9
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Forsyth P A
Department of Clinical Neurosciences and Medicine, Tom Baker Cancer Centre, Calgary, Alberta, Canada.
Wong H
Laing T D
Rewcastle N B
Morris D G
Muzik H
Leco K J
Johnston R N
Brasher P M
Sutherland G
Edwards D R
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Article Info
Journal
British journal of cancer
Abbr.
Br J Cancer
ISSN
0007-0920
DOI
10.1038/sj.bjc.6690291
Published
1999-04-00
Pages
1828-35
Language
English
Region
England
NLM ID
0370635
PMCID
PMC2362801
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.bjc.6690291 PMC Full Text View journal details
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