BCL‐2 promotes migration and invasiveness of human glioma cells

Abstract

Malignant progression in gliomas is correlated with increased migratory capacity which involves metalloproteolytic activity. Here, we report that ectopic expression of BCL-2 in two malignant glioma sublines markedly promoted glioma cell migration from spheroids and invasion into Matrigel-coated membranes. Invasion of fetal rat-brain aggregates was enhanced by BCL-2. Zymography revealed activation of matrix metalloproteinase-2 (MMP-2) in BCL-2-expressing cells. BCL-2 expressing cells showed an increase in MMP-2/-3/-12 (LN-18), and MMP-9/-12 and cell surface urokinase-type plasminogen activator (u-PA) (LN-229) mRNA and a reduction in tissue inhibitors of metalloproteinases (TIMP)-2 mRNA (LN-229). Taken together, we propose a novel function for BCL-2 in the malignant phenotype of glioma cells, that is, to enhance migration and invasion by altering the expression of a set of metalloproteinases and their inhibitors.