DETERMINANTS OF HUMAN ASTROCYTOMA MIGRATION

A unique characteristic of astrocytic malignancies is their frequent d issemination through the brain. Cellular determinants of migration inc lude adhesion to the substratum, restructuring of the actin cytoskelet on to generate motion, and (in the setting of invasion into tissue) se cretion of enzymes for remodeling interstitial space to accommodate fo rward motion of the migrating cell. In order to better understand thes e features in the context of local brain invasion by astrocytoma cells , the adhesion and migratory properties of these cells have been inves tigated in an in vitro monolayer system. Adhesion of 8 different astro cytoma cell lines to different purified human extracellular matrix (EC M) proteins (collagen type IV, cellular fibronectin, laminin, and vitr onectin) revealed that there is no ''astrocytoma-specific'' ECM protei n that consistently leads to high cell binding. Similarly, migration o f astrocytoma cells was found to be variable and dependent on differen t ECM proteins. Laminin was frequently the most permissive for adhesio n and migration. Adhesion to collagen, fibronectin, and vitronectin wa s integrin dependent and could be blocked using anti-beta(i) integrin antibodies; in contrast, attachment to laminin could not be blocked us ing these antibodies. A comparison of adhesion with migration for each of the cell lines on each of the 4 ECM proteins revealed that poor ad hesion was associated with minimal migration and that frequently, high adhesion was correlated with rapid migration. When tested for migrati on on autologous, cell-derived ECM, none of the cell lines were as mig ratory as they were on one of the purified ECM proteins, with the exce ption of SF767 cells. Furthermore, it was found that ECM from SF767 ce lls promoted the migration of other astrocytoma cells. The results fro m this study indicate that migration is a constitutive behavior of gli oma cells which is dependent on, or modified by, the presence or absen ce of permissive ligands in the environment.