Elevated levels of cathepsin B in human glioblastoma cell lines

Degradation of the extracellular matrix is a prerequisite for the invasive phenotype in glioma cells. Several proteases released by invading tumor cel ls seem to participate in the focal degradation of extracellular matrix pro teins. Using enzymatic assays, Western blotting, and Northern blotting tech niques, we investigated whether cathepsin B level was associated with malig nant grade in seven human glioma cell lines. Cathepsin B activity and prote in content levels were higher in glioblastoma cell lines than in anaplastic astrocytoma or low-grade glioma cell lines. Cathepsin B transcripts were o verexpressed in glioblastoma cell lines relative to their expression in ana plastic astrocytoma and low-grade glioma cell lines. Cathepsin B promoter a ctivity and amount of SP-1 complexes were much higher in glioblastoma cell lines than in anaplastic astrocytoma or low-grade glioma cell lines. Finall y, E-64, an inhibitor of cathepsin B, inhibited both cathepsin B enzymatic activity and the invasiveness of glioblastoma cell lines. These results str ongly support a role for cathepsin B in glioblastoma cell lines and suggest that inhibition of cathepsin B activity may be proven useful in cancer the rapy.