No abstract

Invasion and metastasis of certain tumors are accompanied by increased mRNA protein levels and enzymatic activity of cathepsin L. Cathepsin L has also been suggested to play a role in the proteolytic cascades associated with apoptosis. To investigate the role of cathepsin L in brain tumor invasion and apoptosis, the human glioma cell line, IPTP, was stably transfected with full -length antisense and sense cDNA of cathepsin L. Down -regulation of cathepsin L by antisense cDNA significantly impaired ( up to 70% ) glioma cell invasion in vitro and markedly increased glioma cell apoptosis induced by staurosporine. Compared to control and parental cell lines, antisense down -regulation of cathepsin L was associated with an earlier induction of caspase -3 activity. Up -regulation of cathepsin L activity by sense cDNA was associated with reduced apoptosis and later induction of caspase -3 activity. Moreover, down -regulation of cathepsin L lowered the expression of antiapoptotic protein Bcl -2, whereas up -regulation increased the expression of Bcl -2, indicating that cathepsin L acts upstream of caspase -3. These data show that cathepsin L is an important protein mediating the malignancy of gliomas and its inhibition may diminish their invasion and lead to increased tumor cell apoptosis by reducing apoptotic threshold.