CATHEPSIN-B EXPRESSION AND LOCALIZATION IN GLIOMA PROGRESSION AND INVASION

The poor prognosis of human malignant gliomas is due to their invasion and recurrence, the molecular mechanisms of which remain poorly chara cterized. We have accumulated substantial evidence implicating the cys teine protease cathepsin B in human glioma malignancy. Increases in ca thepsin B expression were observed throughout progression. In primary brain tumor tissue, transcript abundance (Northern blot analysis) incr eased in low-grade astrocytoma to high-grade glioblastoma from 3- to 6 -fold, respectively, above normal brain levels. This increase correlat ed with increases in protein abundance (from + to +++) as measured by immunohistochemistry. Furthermore, in glioblastoma cell fines increase s in transcript abundance (ranging from 3- to 12-fold) were accompanie d by increases in enzyme activity (44-133 nmol/min x mg protein). Alte red subcellular localization was observed both immunohistochemically a nd by indirect immunofluorescence confocal microscopy and was found to correlate with increased grade. In addition, this increase in catheps in B expression and altered subcellular localization correlated with h istomorphological invasion and clinical evidence of invasion as detect ed by magnetic resonance imaging. These data support the hypothesis th at cathepsin B plays a role in human glioma progression and invasion.