Gap junction intercellular communication in gliomas is inversely related to cell motility

Gliomas are lethal because of local invasion into brain parenchyma. Glioma cells were isolated from different regions (white matter, gray matter and t umor core) of a glioma-bearing dog brain. Individual clonal cell lines were established from each area, and characterized for growth, migration and ga p junctions. The regional clonal cell lines differed in rates and preferred substrate for migration. Cell lines generated from invaded white matter sh owed stimulated migration on collagen and variable migration on merosin, wh ereas migration of cell lines derived from invaded gray matter showed the r eciprocal responses: stimulation on merosin and inhibition on collagen. Gap junctional communication showed significant degrees of Variation between t he different clones. A direct inverse relationship between the number of ce lls demonstrating gap junctional communication and migration rate of cells away from multicellular spheroids was evident. Glioma cells which have a re duced capacity to connect to each other have an accelerated migration rate onto autologous, glioma-derived matrix. These results suggest that invasive glioma cells suppress autologous cell-to-cell cohesion, partly evident as reduced formation of gap junctions. In addition, glioma cells were stimulat ed to migrate in a dose-dependant manner in response to epidermal growth fa ctor (EGF) coincident with the reduction of Cx43 levels and increased serin e phosphorylation. We speculate that in order for glioma cells to invade lo cally into brain parenchyma they must first detach from neighboring cells ( "let go...let's go" paradigm of invasion). (C) 1999 ISDN. Published by Else vier Science Ltd. All rights reserved.