SUBSTRATES FOR ASTROCYTOMA INVASION

A BETTER UNDERSTANDING of the influences of specific extracellular sub strates, including proteins, glycosaminoglycans, and parenchymal cells , on the invasive behavior of glioma cells would potentially lead to n ovel forms of treatment aimed at confining the tumor. A monolayer, mic roliter scale assay was used to investigate how different substrates i nfluenced glioma migration. Basal or unspecific movement (range, 10-26 0 mu m/d) was determined by observing a panel of seven established hum an glioma cell lines. Migration rates two to five times higher than th is basal activity were referred to as preferential and specific glioma migration; these rates generally occurred on merosin and tenascin. Co llagen, fibronectin, or vitronectin were less supportive of migration, The glioma cells migrated on hyaluronic acid, but they did not migrat e to the extent generally found on the extracellular matrix proteins. Glioma-derived extracellular matrix also served to promote cell migrat ion. This finding implicates a role for either glioma remodeling or sy nthesis of a permissive environment for local dissemination that may b e independent of the constitutive matrix proteins normally found in th e brain. Although the glioma cells were able to migrate over monolayer s of other glioma cells, they were unable to migrate over astrocytes a nd fibroblasts. Our findings indicate that the invasive behavior of gl ioma cells in situ is most likely a consequence of the interplay betwe en the cells' manipulation of the environment and the constitutive lig ands associated with specific regions or structures of the brain.