Selective suppression of cathepsin L by antisense cDNA impairs human brain tumor cell invasion in vitro and promotes apoptosis

Levicar, Natasa and Dewey, Ricardo A. and Daley, Emma and Bates, Timothy E. and Davies, Derek and Kos, Janko and Pilkington, Geoffrey J. and Lah, Tamara T. (2003) Selective suppression of cathepsin L by antisense cDNA impairs human brain tumor cell invasion in vitro and promotes apoptosis. Cancer Gene Therapy, 10 (2). pp. 141-51. ISSN 0929-1903

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Item Type:Article
Item Status:Live Archive

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.

Additional Information:PMID: 12536203
Keywords:Cathepsin, antisense cDNA, cell invasion, apoptosis, IPTP, Brain Tumour
Subjects:A Medicine and Dentistry > A100 Pre-clinical Medicine
B Subjects allied to Medicine > B131 Cellular Pathology
B Subjects allied to Medicine > B140 Neuroscience
B Subjects allied to Medicine > B132 Pathobiology
A Medicine and Dentistry > A300 Clinical Medicine
B Subjects allied to Medicine > B130 Pathology
Divisions:College of Science > School of Life Sciences
ID Code:5243
Deposited On:08 Jun 2013 08:28

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