Malignant progression in gliomas is correlated with increased migratory cap
acity which involves metalloproteolytic activity. Here, we report that ecto
pic expression of BCL-2 in two malignant glioma sublines markedly promoted
glioma cell migration from spheroids and invasion into Matrigel-coated memb
ranes, Invasion of fetal rat-brain aggregates was enhanced by BCL-2, Zymogr
aphy revealed activation of matrix metalloproteinase-2 (MMP-2) in BCL-2-exp
ressing cells. BCL-2 expressing cells showed an increase in MMP-2/-3/-12 (L
N-18), and MMP-9/-12 and cell surface urokinase-type plasminogen activator
(u-PA) (LN-229) mRNA and a reduction in tissue inhibitors of metalloprotein
ases (TIMP)-2 mRNA (LN-229). Taken together, we propose a novel function fo
r BCL-2 in the malignant phenotype of glioma cells, that is, to enhance mig
ration and invasion by altering the expression of a set of metalloproteinas
es and their inhibitors. (C) 1998 Federation of European Biochemical Societ
ies.