Human malignant gliomas secrete a factor that increases brain capillary permeability: role in peritumoural brain...

The effect of conditioned media obtained from two human malignant gliomas and normal human glia on rat brain capillary permeability was investigated by measuring the entry of 14C-aminoisobutyric acid by a quantitative autoradiographic method. Conditioned media were concentrated 50-fold to create SUP-C. The SUP-C contained proteins with a molecular weight greater than 10 kD. The SUP-C from glioma cells markedly increased brain capillary permeability, whereas that from normal glial cells did not. The activity of capillary permeability factor in the SUP-C was significantly inhibited by pretreatment of animals with dexamethasone or BW755C (lipoxygenase inhibitor), but not with indomethacin. On the other hand, coincubation of glioma cells with dexamethasone produced SUP-C whose capillary permeability activity was about one and a half times greater than that without dexamethasone. These results indicate that human malignant glioma cells secrete a protein factor that increases brain capillary permeability. Glucocorticoids inhibit the effect of the factor by directly acting on capillary endothelial cells, possibly through the inhibition of phospholipase A2 activity, resulting in a decrease of lipoxygenase rather than cyclo-oxygenase products.