Abstract
Glioblastoma cells infiltrate brain tissue and migrate preferentially along white matter fibre tracts, an environment that is highly inhibitory to the migration of astrocytes and the growth of neurites because of the presence of specific inhibitory proteins. In vitro, spreading and migration of rat C6 glioma cells on a CNS (central nervous system) myelin substrate is correlated with and dependent on the presence of a metalloprotease. This membrane-bound metalloendoprotease exhibits a blocker profile different from known proteases. Pretreatment of CNS myelin or of a highly purified CNS myelin component, the inhibitory protein bNI-220, with C6 metalloproteolytic activity converts these non-permissive substrates into permissive environments for astrocytes and fibroblasts, indicating that this C6 cell-derived metalloprotease may inactivate myelin-associated inhibitory proteins. Antibodies were raised in chicken against fractions enriched in metalloproteolytic activity; these antibodies were able to inhibit specifically spreading and migration of C6 glioma cells on a CNS myelin substrate, as well as the invasion of C6 cells into adult rat optic nerve explants in vitro. These results suggest a crucial involvement of a membrane-bound metalloprotease in the mechanisms of C6 glioma migration and infiltration of brain tissue by proteolytic inactivation of the neurite growth inhibitory proteins present in CNS myelin.
Highlights
MethodsMolecular weiaht standards for gel filtration and all other chemicals wxere purchased from Sigma Chemical Co
Summary Glioblastoma cells infiltrate brain tissue and migrate preferentially along white matter fibre tracts, an environment that is highly inhibitory to the migration of astrocytes and the growth of neurites because of the presence of specific inhibitory proteins
Antibodies were raised in chicken against fractions enriched in metalloproteolytic activity: these antibodies were able to inhibit spreading and migration of C6 glioma cells on a CNS myelin substrate. as well as the invasion of C6 cells into aduft rat optic nerve explants in vitro
Summary
Molecular weiaht standards for gel filtration and all other chemicals wxere purchased from Sigma Chemical Co The tetrapeptide carbobenzox\--phe-ala-phe-t\-r-amide >-as s5ynthesized by Bachem
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