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Membrane-type 1 Matrix Metalloprotease (MT1-MMP) Enables Invasive Migration of Glioma Cells in Central Nervous System White Matter

Invasive glioma cells migrate preferentially along central nervous system (CNS) white matter fiber tracts irrespective of the fact that CNS myelin contains proteins that inhibit cell migration and neurite outgrowth. Previous work has demonstrated that to migrate on a myelin substrate and to overcome...

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Autores principales: Beliën, Ann T.J., Paganetti, Paolo A., Schwab, Martin E.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1999
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2132902/
https://www.ncbi.nlm.nih.gov/pubmed/9922462
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author Beliën, Ann T.J.
Paganetti, Paolo A.
Schwab, Martin E.
author_facet Beliën, Ann T.J.
Paganetti, Paolo A.
Schwab, Martin E.
author_sort Beliën, Ann T.J.
collection PubMed
description Invasive glioma cells migrate preferentially along central nervous system (CNS) white matter fiber tracts irrespective of the fact that CNS myelin contains proteins that inhibit cell migration and neurite outgrowth. Previous work has demonstrated that to migrate on a myelin substrate and to overcome its inhibitory effect, rat C6 and human glioblastoma cells require a membrane-bound metalloproteolytic activity (C6-MP) which shares several biochemical and pharmacological characteristics with MT1-MMP. We show now that MT1-MMP is expressed on the surface of rat C6 glioblastoma cells and is coenriched with C6-MP activity. Immunodepletion of C6-MP activity is achieved with an anti–MT1-MMP antibody. These data suggest that MT1-MMP and the C6-MP are closely related or identical. When mouse 3T3 fibroblasts were transfected with MT1-MMP they acquired the ability to spread and migrate on the nonpermissive myelin substrate and to infiltrate into adult rat optic nerve explants. MT1-MMP–transfected fibroblasts and C6 glioma cells were able to digest bNI-220, one of the most potent CNS myelin inhibitory proteins. Plasma membranes of both MT1-MMP–transfected fibroblasts and C6 glioma cells inactivated inhibitory myelin extracts, and this activity was sensitive to the same protease inhibitors. Interestingly, pretreatment of CNS myelin with gelatinase A/MMP-2 could not inactivate its inhibitory property. These data imply an important role of MT1-MMP in spreading and migration of glioma cells on white matter constituents in vitro and point to a function of MT1-MMP in the invasive behavior of malignant gliomas in the CNS in vivo.
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spelling pubmed-21329022008-05-01 Membrane-type 1 Matrix Metalloprotease (MT1-MMP) Enables Invasive Migration of Glioma Cells in Central Nervous System White Matter Beliën, Ann T.J. Paganetti, Paolo A. Schwab, Martin E. J Cell Biol Regular Articles Invasive glioma cells migrate preferentially along central nervous system (CNS) white matter fiber tracts irrespective of the fact that CNS myelin contains proteins that inhibit cell migration and neurite outgrowth. Previous work has demonstrated that to migrate on a myelin substrate and to overcome its inhibitory effect, rat C6 and human glioblastoma cells require a membrane-bound metalloproteolytic activity (C6-MP) which shares several biochemical and pharmacological characteristics with MT1-MMP. We show now that MT1-MMP is expressed on the surface of rat C6 glioblastoma cells and is coenriched with C6-MP activity. Immunodepletion of C6-MP activity is achieved with an anti–MT1-MMP antibody. These data suggest that MT1-MMP and the C6-MP are closely related or identical. When mouse 3T3 fibroblasts were transfected with MT1-MMP they acquired the ability to spread and migrate on the nonpermissive myelin substrate and to infiltrate into adult rat optic nerve explants. MT1-MMP–transfected fibroblasts and C6 glioma cells were able to digest bNI-220, one of the most potent CNS myelin inhibitory proteins. Plasma membranes of both MT1-MMP–transfected fibroblasts and C6 glioma cells inactivated inhibitory myelin extracts, and this activity was sensitive to the same protease inhibitors. Interestingly, pretreatment of CNS myelin with gelatinase A/MMP-2 could not inactivate its inhibitory property. These data imply an important role of MT1-MMP in spreading and migration of glioma cells on white matter constituents in vitro and point to a function of MT1-MMP in the invasive behavior of malignant gliomas in the CNS in vivo. The Rockefeller University Press 1999-01-25 /pmc/articles/PMC2132902/ /pubmed/9922462 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Regular Articles
Beliën, Ann T.J.
Paganetti, Paolo A.
Schwab, Martin E.
Membrane-type 1 Matrix Metalloprotease (MT1-MMP) Enables Invasive Migration of Glioma Cells in Central Nervous System White Matter
title Membrane-type 1 Matrix Metalloprotease (MT1-MMP) Enables Invasive Migration of Glioma Cells in Central Nervous System White Matter
title_full Membrane-type 1 Matrix Metalloprotease (MT1-MMP) Enables Invasive Migration of Glioma Cells in Central Nervous System White Matter
title_fullStr Membrane-type 1 Matrix Metalloprotease (MT1-MMP) Enables Invasive Migration of Glioma Cells in Central Nervous System White Matter
title_full_unstemmed Membrane-type 1 Matrix Metalloprotease (MT1-MMP) Enables Invasive Migration of Glioma Cells in Central Nervous System White Matter
title_short Membrane-type 1 Matrix Metalloprotease (MT1-MMP) Enables Invasive Migration of Glioma Cells in Central Nervous System White Matter
title_sort membrane-type 1 matrix metalloprotease (mt1-mmp) enables invasive migration of glioma cells in central nervous system white matter
topic Regular Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2132902/
https://www.ncbi.nlm.nih.gov/pubmed/9922462
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