Direct gap junction communication between malignant glioma cells and astrocytes

Gap junctions are intercellular channels that connect the interiors of coup led cells. We sought to determine the extent to which malignant glioma cell s form gap junction channels with astrocytes from either adult human brain or rat forebrain, The astrocytic gap junction protein, connexin 43 (Cx43), was identified in immunoreactive plaques at areas of cell-to-cell contact b etween cocultured glioma cells and astrocytes, These gap junction plaques w ere composed of functional channels, because extensive dye coupling was evi dent between the glioma cells and astrocytes from both human and rat brain, Calcium signaling was also readily transmitted from glioma cells to astroc ytes and vice versa,In live rat brain, injection of glioma cells prelabeled with the gap junction tracer, dicarboxy-dichlorofluorescein, revealed exte nsive dye transfer to host cells, demonstrating that malignant glioma cells directly couple with normal brain cells, These observations suggest that i ntercellular communication via gap Junctions may play a role in regulating cellular interactions during tumor invasion, In fact, the presence of gap j unctions between astrocytes and glioma cells was sufficient to induce trans formation of astrocytic phenotype, Astrocytes cocultured with C6 glioma cel ls overexpressing Cx43 were significantly smaller and expressed a lower lev el of glial fibrillary acidic protein than astrocytes cocultured with other wise identical mock-transfected, gal, junction-deficient CG cells. Thus, di rect cellular coupling with glioma cells result in a phenotypic transformat ion of astrocytes that may contribute to the susceptibility of surrounding tissue to glioma invasion.