Cathepsin B and glioma invasion

Increased expression of cathepsin B has been reported in a number of human and animal tumors. This has also been observed in human gliomas where incre ases in cathepsin B mRNA, protein, activity and secretion parallel malignan t progression. In the present study, we showed that cathepsin B was directl y involved in glioma cell invasion. Activity of cathepsin B was an order of magnitude higher in glioma tissue than in matched normal brain. Inhibitors of cysteine proteases reduced invasion of glioma cells in two in vitro mod els: invasion through Matrigel and infiltration of a glioma spheroid into a normal brain aggregate. Glioma spheroids expressed higher levels of cathep sin B than did monolayers and the ability of subclones differing in catheps in B activity to infiltrate normal brain aggregates paralleled their cathep sin B activity. We confirmed that intracellular staining for cathepsin B oc curs at the cell periphery and in cell processes and observed extracellular staining on the cell surface. In addition, we demonstrated that intracellu lar cathepsin B located at the cell periphery and in processes was active. The cell surface cathepsin B colocalized with areas of degradation of an ex tracellular matrix component. We hypothesize that the increased expression of active cathepsin B in gliomas leads to increases in invasion bz vitro an d in vivo and have developed a xenotransplant model in which this hypothesi s can be tested. (C) 1999 ISDN. Published by Elsevier Science Ltd All right s reserved.