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 cells seem to participate in the focal degradation of extracellular matrix proteins. Using enzymatic assays, Western blotting, and Northern blotting techniques, we investigated whether cathepsin B level was associated with malignant grade in seven human glioma cell lines. Cathepsin B activity and protein content levels were higher in glioblastoma cell lines than in anaplastic astrocytoma or low-grade glioma cell lines. Cathepsin B transcripts were overexpressed in glioblastoma cell lines relative to their expression in anaplastic astrocytoma and low-grade glioma cell lines. Cathepsin B promoter activity and amount of SP-1 complexes were much higher in glioblastoma cell lines than in anaplastic astrocytoma or low-grade glioma cell lines. Finally, E-64, an inhibitor of cathepsin B, inhibited both cathepsin B enzymatic activity and the invasiveness of glioblastoma cell lines. These results strongly support a role for cathepsin B in glioblastoma cell lines and suggest that inhibition of cathepsin B activity may be proven useful in cancer therapy.
Konduri
S
S
Division of Cancer Biology, Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine at Peoria, One Illini Drive, Peoria, IL 61656, USA.
Lakka
S S
SS
Tasiou
A
A
Yanamandra
N
N
Gondi
C S
CS
Dinh
D H
DH
Olivero
W C
WC
Gujrati
M
M
Rao
J S
JS
D015152:Blotting, Northern; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000201:enzymology*; D002401:Cathepsin B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D002999:Clone Cells; D003094:Collagen / Q000737:chemistry; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004338:Drug Combinations; D005909:Glioblastoma / Q000201:enzymology*; D006801:Humans; D007797:Laminin / Q000737:chemistry; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011509:Proteoglycans / Q000737:chemistry; D014407:Tumor Cells, Cultured / Q000201:enzymology*; D001616:beta-Galactosidase / Q000378:metabolism
D015853:Cysteine Proteinase Inhibitors; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D015500:Chloramphenicol O-Acetyltransferase; D001616:beta-Galactosidase; D002401:Cathepsin B; D007930:Leucine; C024974:E 64