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

Publication ,  Journal Article
Mohanam, S; Jasti, SL; Kondraganti, SR; Chandrasekar, N; Lakka, SS; Kin, Y; Fuller, GN; Yung, AW; Kyritsis, AP; Dinh, DH; Olivero, WC; Rao, JS ...
Published in: Oncogene
June 21, 2001

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.

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Published In

Oncogene

DOI

ISSN

0950-9232

Publication Date

June 21, 2001

Volume

20

Issue

28

Start / End Page

3665 / 3673

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Transfection
  • Spheroids, Cellular
  • Rats, Sprague-Dawley
  • Rats
  • RNA, Messenger
  • Oncology & Carcinogenesis
  • Neoplasm Transplantation
  • Neoplasm Invasiveness
  • Mice, Nude
 

Citation

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Mohanam, S., Jasti, S. L., Kondraganti, S. R., Chandrasekar, N., Lakka, S. S., Kin, Y., … 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
Mohanam, S., S. L. Jasti, S. R. Kondraganti, N. Chandrasekar, S. S. Lakka, Y. Kin, G. N. Fuller, et al. “Down-regulation of cathepsin B expression impairs the invasive and tumorigenic potential of human glioblastoma cells.Oncogene 20, no. 28 (June 21, 2001): 3665–73. https://doi.org/10.1038/sj.onc.1204480.
Mohanam S, Jasti SL, Kondraganti SR, Chandrasekar N, Lakka SS, Kin Y, et al. Down-regulation of cathepsin B expression impairs the invasive and tumorigenic potential of human glioblastoma cells. Oncogene. 2001 Jun 21;20(28):3665–73.
Mohanam, S., et al. “Down-regulation of cathepsin B expression impairs the invasive and tumorigenic potential of human glioblastoma cells.Oncogene, vol. 20, no. 28, June 2001, pp. 3665–73. Pubmed, doi:10.1038/sj.onc.1204480.
Mohanam S, Jasti SL, Kondraganti SR, Chandrasekar N, Lakka SS, Kin Y, Fuller GN, Yung AW, Kyritsis AP, Dinh DH, Olivero WC, Gujrati M, Ali-Osman F, Rao JS. Down-regulation of cathepsin B expression impairs the invasive and tumorigenic potential of human glioblastoma cells. Oncogene. 2001 Jun 21;20(28):3665–3673.

Published In

Oncogene

DOI

ISSN

0950-9232

Publication Date

June 21, 2001

Volume

20

Issue

28

Start / End Page

3665 / 3673

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Transfection
  • Spheroids, Cellular
  • Rats, Sprague-Dawley
  • Rats
  • RNA, Messenger
  • Oncology & Carcinogenesis
  • Neoplasm Transplantation
  • Neoplasm Invasiveness
  • Mice, Nude