Differential expression and localization of TIMP-1 and TIMP-4 in human gliomas

Studies have suggested that an imbalance of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) may contribute to the malignant phenotype of gliomas. In this study, we have undertaken a detailed analysis of expression of the TIMP family in normal human brain and mali...

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Bibliographic Details
Published in:British journal of cancer 2001-07, Vol.85 (1), p.55-63
Main Authors: GROFT, L. L, MUZIK, H, REWCASTLE, N. B, JOHNSTON, R. N, KNÄUPER, V, LAFLEUR, M. A, FORSYTH, P. A, EDWARDS, D. R
Format: Article
Language:English
Subjects:
Biological and medical sciences
Brain Neoplasms - enzymology
Brain Neoplasms - genetics
Brain Neoplasms - metabolism
Brain Neoplasms - pathology
Cancer research
Enzyme Activation - drug effects
Enzyme Precursors - metabolism
Enzymes
Gelatinases - metabolism
Gene Expression Regulation, Neoplastic
Genotype & phenotype
Glioma - enzymology
Glioma - genetics
Glioma - metabolism
Glioma - pathology
Humans
In Situ Hybridization
Localization
Medical research
Medical sciences
Metalloendopeptidases - metabolism
Metastasis
Neoplasm Invasiveness
Neurology
Neurosciences
Regular
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - biosynthesis
RNA, Messenger - genetics
Tissue Inhibitor of Metalloproteinase-1 - biosynthesis
Tissue Inhibitor of Metalloproteinase-1 - genetics
Tissue Inhibitor of Metalloproteinase-4
Tissue Inhibitor of Metalloproteinases - biosynthesis
Tissue Inhibitor of Metalloproteinases - genetics
Tissue Inhibitor of Metalloproteinases - pharmacology
Tumor Cells, Cultured
Tumors of the nervous system. Phacomatoses
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Summary:Studies have suggested that an imbalance of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) may contribute to the malignant phenotype of gliomas. In this study, we have undertaken a detailed analysis of expression of the TIMP family in normal human brain and malignant gliomas at both the mRNA and protein level. Reverse transcription-PCR (RT-PCR) analyses of total RNA from surgical tumour specimens revealed unique expression patterns for the 4 members of the TIMP family, with TIMP-1 and -4 showing positive and negative correlations, respectively, with glioma malignancy. By RT-PCR, TIMP-2 and TIMP-3 expression did not change with tumour grade. In situ hybridization localized TIMP-1 to glial tumour cells and also to the surrounding tumour vasculature. TIMP-4 transcripts were predominantly localized to tumour cells, though minor expression was found in vessels. Recombinant TIMP-4 reduced invasion of U251 glioma cells through Matrigel, and U87 clones overexpressing TIMP-4 showed reduced invasive capacity in vitro. TIMP-4, but not TIMP-1, blocked Membrane Type-1-MMP-mediated progelatinase-A (MMP-2) activation in human umbilical vein endothelial cells. The differential expression and localization of individual TIMPs may contribute to the pathophysiology of human malignant gliomas, particularly with regard to tumour vascularization.
ISSN:0007-0920
1532-1827
DOI:10.1054/bjoc.2001.1854