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Modulation of cystatin C expression impairs the invasive and tumorigenic potential of human glioblastoma cells

Oncogene volume 21, pages 8705–8712 (2002)Cite this article

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.

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Acknowledgements

This work was supported in part by a National Institute for Health grant CA 76350 to Jasti S Rao.

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Authors and Affiliations

  1. Division of Cancer Biology, Department of Biomedical and Therapeutic Sciences, University of Illinois, Peoria, Illinois, USA

    Santhi D Konduri, Niranjan Yanamandra, Arun Joseph & Jasti S Rao

  2. Department of Neurosurgery, University of Illinois, Peoria, Illinois, USA

    Khawar Siddique, Dzung H Dinh, William C Olivero & Jasti S Rao

  3. Department of Neuro-pathology, University of Illinois, Peoria, Illinois, USA

    Meena Gujrati

  4. Department of Propedeutic Surgery, Athens University School of Medicine, Athens, Greece

    Gregory Kouraklis

  5. Department of Ophthalmology & Visual Sciences and Human Genetics, WK Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan, USA

    Amand Swaroop

  6. Department of Neurology, University of Ioannina School of Medicine, Ioannina, Greece

    Athanassios P Kyritsis

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  1. Santhi D Konduri
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Correspondence to Jasti S Rao.

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Konduri, S., Yanamandra, N., Siddique, K. et al. Modulation of cystatin C expression impairs the invasive and tumorigenic potential of human glioblastoma cells. Oncogene 21, 8705–8712 (2002). https://doi.org/10.1038/sj.onc.1205949

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