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

Groft, L. L., Muzik, H., Johnston, R. N., Knauper, Vera ORCID: https://orcid.org/0000-0002-3965-9924, Lafleur, M. A., Forsyth, P. A. and Edwards, D. R. 2001. Differential expression and localization of TIMP-1 and TIMP-4 in human gliomas. British Journal of Cancer 85 (1) , pp. 55-63. 10.1054/bjoc.2001.1854

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Abstract

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. © 2001 Cancer Research Campaign

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Dentistry
Publisher:	Springer Nature [academic journals on nature.com]
ISSN:	0007-0920
Date of Acceptance:	20 March 2001
Last Modified:	14 Sep 2023 15:48
URI:	https://orca.cardiff.ac.uk/id/eprint/161599

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