Author/Editor		Levičar, Nataša; Dewey, Ricardo A; Daley, Em,ma; Bates, Timothy E; Davies, Derek; Kos, Janko; Pilkington, Geoffrey J; Lah, Tamara T
Title		Selective suppression of cathepsin L by antisense cDNA impairs human brain tumor cell invasion in vitro and promotes apoptosis
Type		članek
Source		Cancer Gene Ther
Vol. and No.		Letnik 10
Publication year		2003
Volume		str. 141-51
Language		eng
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 Bel-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.
Descriptors		CATHEPSINS GLIOBLASTOMA NEOPLASM INVASIVENESS APOPTOSIS DNA, ANTISENSE STAUROSPORINE TRANSFECTION ENZYME-LINKED IMMUNOSORBENT ASSAY FLOW CYTOMETRY PROTO-ONCOGENE PROTEINS C-BCL-2