EXPRESSION OF CATHEPSIN-D DURING THE PROGRESSION OF HUMAN GLIOMAS

Recent studies suggest that aspartic proteinase cathepsin D may be imp licated in tumor invasion and metastasis either directly by degrading extracellular matrix or indirectly by activating the cysteine proteina ses such as procathepsin B, H, and L to mature forms or by inactivatin g cysteine proteinase inhibitors. In this study we determined for the first time whether increased levels of cathepsin D correlate with glio ma progression by enzymatic assay, ELISA, and western blotting. Cathep sin D activity and content were higher in anaplastic astrocytoma and i n glioblastoma tissue extracts especially when compared to normal brai n tissue and low-grade gliomas. There was a significantly increased in tensity of an M(r) 29 000 band in glioblastoma and anaplastic astrocyt oma compared to low-grade glioma and normal brain tissue on Western bl otting analysis using its specific antibodies. Cathepsin D antibody in hibited the invasion of glioblastoma cell lines in a dose-dependent ma nner. These results suggest that the expression oi cathepsin D is dram atically upregulated in malignant gliomas, and that its increase corre lates with the malignant progression of human gliomas in vivo.