Overexpression and localization of cathepsin B during the progression of human gliomas.
Degradation of the extracellular matrix is a prerequisite for acquisition of the invasive phenotype. Several proteinases released by invading tumor cells appear to participate in the focal degradation of extracellular matrix proteins. Using an enzyme-linked immunosorbent assay, enzymatic assays, Western and Northern blotting techniques, we determined whether increased levels of the cysteine protease cathepsin B correlated with the progression and invasion of human gliomas. The amount of cathepsin B activity and protein content were highest in glioblastomas, lower in anaplastic astrocytomas and lowest in normal brain tissue and low-grade gliomas. There were significantly higher amounts of M(r) 25,000 and 26,000 bands in glioblastoma and anaplastic astrocytoma than in normal brain and low-grade glioma tissue extracts as determined by Western blotting with anti-cathepsin antibodies. In addition, cathepsin B transcripts were overexpressed in anaplastic astrocytoma (about two- to three-fold), in glioblastoma (about eight- to 10-fold), compared with normal brain tissue and low-grade glioma. Immunohistochemical staining for cathepsin B showed intense immunoreactivity in tumor and endothelial cells of glioblastomas and anaplastic astrocytomas but only weak immunoreactivity in low-grade glioma and normal brain tissues. Therefore, we conclude that cathepsin B expression is greatest in highly malignant astrocytomas, especially in glioblastomas, and is correlated with the malignant progression of astrocytomas.
Sivaparvathi
M
M
Department of Neurosurgery, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Sawaya
R
R
Wang
S W
SW
Rayford
A
A
Yamamoto
M
M
Liotta
L A
LA
Nicolson
G L
GL
Rao
J S
JS
D015152:Blotting, Northern; D015153:Blotting, Western; D001921:Brain / Q000201:enzymology; D001932:Brain Neoplasms / Q000201:enzymology*; D002401:Cathepsin B / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000201:enzymology*; D006801:Humans; D007150:Immunohistochemistry; D012334:RNA, Neoplasm / Q000378:metabolism; D015854:Up-Regulation
D012334:RNA, Neoplasm; D002401:Cathepsin B