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PMID: 9922462 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Membrane-type 1 matrix metalloprotease (MT1-MMP) enables invasive migration of glioma cells in central nervous system white matter.

The Journal of cell biology ·Vol. 144 ·No. 2 ·1999-01-25 ·Pages 373-84

Beliën AT, Paganetti PA, Schwab ME

Abstract

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.

MeSH Terms
3T3 Cells Animals Antibodies, Monoclonal/immunology Cell Extracts Cell Membrane/metabolism Cell Movement Central Nervous System/pathology Enzyme Activation Gelatinases/metabolism Glioblastoma/pathology Glioma/pathology Humans Matrix Metalloproteinase 14 Matrix Metalloproteinase 2 Matrix Metalloproteinases, Membrane-Associated Metalloendopeptidases/antagonists & inhibitors,genetics,metabolism Mice Myelin Sheath/physiology Neoplasm Invasiveness Optic Nerve/physiology Protease Inhibitors/pharmacology Rats Transfection Tumor Cells, Cultured
Chemicals
Antibodies, Monoclonal Cell Extracts Mmp14 protein, mouse Protease Inhibitors Gelatinases Matrix Metalloproteinases, Membrane-Associated Metalloendopeptidases Matrix Metalloproteinase 2 Matrix Metalloproteinase 14
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Beliën A T
Brain Research Institute, University of Zurich and Swiss Federal Institute of Technology, 8057 Zurich, Switzerland. [email protected]
Paganetti P A
Schwab M E
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.144.2.373
Email
[email protected]
Published
1999-01-25
Pages
373-84
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2132902
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.144.2.373 PMC Full Text View journal details
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