Expression of cathepsin D during the progression of human gliomas.
Recent studies suggest that aspartic proteinase cathepsin D may be implicated in tumor invasion and metastasis either directly by degrading extracellular matrix or indirectly by activating the cysteine proteinases such as procathepsin B, H, and L to mature forms or by inactivating cysteine proteinase inhibitors. In this study we determined for the first time whether increased levels of cathepsin D correlate with glioma progression by enzymatic assay, ELISA, and western blotting. Cathepsin D activity and content were higher in anaplastic astrocytoma and in glioblastoma tissue extracts especially when compared to normal brain tissue and low-grade gliomas. There was a significantly increased intensity of an M(r) 29,000 band in glioblastoma and anaplastic astrocytoma compared to low-grade glioma and normal brain tissue on Western blotting analysis using its specific antibodies. Cathepsin D antibody inhibited the invasion of glioblastoma cell lines in a dose-dependent manner. These results suggest that the expression of cathepsin D is dramatically upregulated in malignant gliomas, and that its increase correlates with the malignant progression of human gliomas in vivo.
Sivaparvathi
M
M
Department of Neurosurgery, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Sawaya
R
R
Chintala
S K
SK
Go
Y
Y
Gokaslan
Z L
ZL
Rao
J S
JS
D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism*; D002402:Cathepsin D / Q000378:metabolism*; D005910:Glioma / Q000378:metabolism*; D006801:Humans
D002402:Cathepsin D