Down-regulation of cathepsin B expression impairs the invasive and tumorigenic potential of human glioblastoma cells

Sanjeeva Mohanam, Sushma L. Jasti, Sudha R. Kondraganti, Nirmala Chandrasekar, Sajani S. Lakka, Yoshiaki Kin, Gregory N. Fuller, Alfred W K Yung, Anthanassios P. Kyritsis, Dzung H. Dinh, William C. Olivero, Meena Gujrati, Francis Ali-Osman, Jasti S. Rao

Research output: Contribution to journalArticle

Abstract

Increases in abundance of cathepsin B transcript and protein correlate with increases in tumor grade and alterations in subcellular localization and activity of cathepsin B. The enzyme is able to degrade the components of the extracellular matrix (ECM) and activate other proteases capable of degrading ECM. To investigate the role played by this protease in the invasion of brain tumor cells, we transfected SNB19 human glioblastoma cells with a plasmid containing cathepsin B cDNA in antisense orientation. Control cells were transfected with vector alone. Clones expressing antisense cathepsin B cDNA exhibited significant reductions in cathepsin B mRNA, enzyme activity and protein compared to controls. Matrigel Invasion assay showed that the antisense-transfected cells had a markedly diminished invasiveness compared with controls. When tumor spheroids containing antisense transfected SNB19 cells expressing reduced cathepsin B were co-cultured with fetal rat brain aggregates, invasion of fetal rat brain aggregates was significantly reduced. Green Fluorescent Protein (GFP) expressing parental cells and antisense transfectants were generated for detection in mouse brain tissue without any post-chemical treatment. Intracerebral injection of SNB19 stable antisense transfectants resulted in reduced tumor formation in nude mice. These results strongly support a role for cathepsin B in the invasiveness of human glioblastoma cells and suggest cathepsin B antisense may prove useful in cancer therapy.

Original languageEnglish (US)
Pages (from-to)3665-3673
Number of pages9
JournalOncogene
Volume20
Issue number28
DOIs
StatePublished - Jun 21 2001

Keywords

  • Cathepsin B
  • Glioblastoma
  • Invasion

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Mohanam, S., Jasti, S. L., Kondraganti, S. R., Chandrasekar, N., Lakka, S. S., Kin, Y., Fuller, G. N., Yung, A. W. K., Kyritsis, A. P., Dinh, D. H., Olivero, W. C., Gujrati, M., Ali-Osman, F., & Rao, J. S. (2001). Down-regulation of cathepsin B expression impairs the invasive and tumorigenic potential of human glioblastoma cells. Oncogene, 20(28), 3665-3673. https://doi.org/10.1038/sj.onc.1204480