SUBSTRATES FOR ASTROCYTOMA INVASION

A BETTER UNDERSTANDING of the influences of specific extracellular substrates, including proteins, glycosaminoglycans, and parenchymal cells, on the invasive behavior of glioma cells would potentially lead to novel forms of treatment aimed at confining the tumor. A monolayer, microliter scale assay was used to investigate how different substrates influenced glioma migration. Basal or unspecific movement (range, 10-260 mu m/d) was determined by observing a panel of seven established human glioma cell lines. Migration rates two to five times higher than this basal activity were referred to as preferential and specific glioma migration; these rates generally occurred on merosin and tenascin. Collagen, fibronectin, or vitronectin were less supportive of migration, The glioma cells migrated on hyaluronic acid, but they did not migrate to the extent generally found on the extracellular matrix proteins. Glioma-derived extracellular matrix also served to promote cell migration. This finding implicates a role for either glioma remodeling or synthesis of a permissive environment for local dissemination that may be independent of the constitutive matrix proteins normally found in the brain. Although the glioma cells were able to migrate over monolayers of other glioma cells, they were unable to migrate over astrocytes and fibroblasts. Our findings indicate that the invasive behavior of glioma cells in situ is most likely a consequence of the interplay between the cells' manipulation of the environment and the constitutive ligands associated with specific regions or structures of the brain.