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| Original Paper |
| Modulation of cystatin C expression impairs the invasive and tumorigenic potential of human glioblastoma cells |
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| Santhi D Konduri1, Niranjan Yanamandra1, Khawar Siddique2, Arun Joseph1, Dzung H Dinh2, William C Olivero2, Meena Gujrati3, Gregory Kouraklis4, Amand Swaroop5, Athanassios P Kyritsis6 and Jasti S Rao1,2 |
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1Division of Cancer Biology, Department of Biomedical and Therapeutic Sciences, University of Illinois, Peoria, Illinois, USA
2Department of Neurosurgery, University of Illinois, Peoria, Illinois, USA
3Department of Neuro-pathology, University of Illinois, Peoria, Illinois, USA
4Department of Propedeutic Surgery, Athens University School of Medicine, Athens, Greece
5Department of Ophthalmology & Visual Sciences and Human Genetics, WK Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan, USA
6Department of Neurology, University of Ioannina School of Medicine, Ioannina, Greece
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Correspondence to: J S Rao, Division of Cancer Biology, Department of Biomedical and Therapeutic Sciences and Department of Neurosurgery, Box 1649, University of Illinois, College of Medicine at Peoria, Peoria, IL 61656, USA; E-mail: jsrao@uic.edu |
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| Abstract |
| Increases in the abundance of cathepsin B transcript and protein with increased tumor grade and changes in subcellular localization and activity of this enzyme. We observed progressive reductions in levels of the protease inhibitor cystatin C, an inhibitor of cathepsin B with corresponding increases in the malignancy of glioma cell lines, implying an inverse correlation between cystatin C and tumor grade. To investigate the role of cystatin C in the invasion of brain tumor cells, we stably transfected SNB19 glioblastoma cells with either a 0.4-kb cDNA construct of human cystatin C in the sense orientation or an empty vector. Clones expressing sense-cystatin C cDNA had higher cystatin C mRNA and protein levels than did control cells. Sense-transfected cells were also markedly less invasive than control cells in a Matrigel invasion assay and in a coculture assay of SNB19 spheroids and fetal rat brain aggregates. Finally, the sense-transfected cells did not form tumors in nude mice upon intracerebral injection. These results strongly implicate cystatin C in the invasiveness of human glioblastoma cells and suggest that sense transcripts of cystatin C may prove useful in cancer therapy. Oncogene (2002) 21, 8705-8712. doi:10.1038/sj.onc.1205949 |
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| Keywords |
| glioma; invasion; cathepsin B; cystatin C |
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| Received 9 April 2002; revised 31 July 2002; accepted 7 August 2002 |
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| 12 December 2002, Volume 21, Number 57, Pages 8705-8712 |
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