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Blockade of cathepsin B expression in human glioblastoma cells is associated with suppression of angiogenesis

Oncogene volume 23, pages 2224–2230 (2004)Cite this article

Abstract

The cysteine proteinase cathepsin B has been implicated in tumor progression by virtue of its increased mRNA and protein levels, as well as its localization at the invading front of the tumor. In this study, we examined whether blocking cathepsin B expression in human glioblastoma SNB19 cells affects angiogenesis. Stable transfectants of human glioblastoma cells with a plasmid containing antisense cathepsin B cDNA showed decreased migration rates in wound- and spheroid-migration assays. Analysis showed a reduction in VEGF protein and MMP-9 activity in the cathepsin B antisense cDNA-transfected cells. Regarding angiogenesis in vitro, we found that the conditioned medium of glioblastoma cells with downregulated cathepsin B expression reduced cell–cell interaction of human microvascular endothelial cells, resulting in the disruption of capillary-like network formation. Furthermore, a marked reduction in microvasculature development was seen in an in vivo dorsal air sac assay of glioblastoma cells with downregulated cathepsin B expression. Taken together, these results provide evidence that inhibition of cathepsin B expression can suppress glioblastoma-induced neovascularization.

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Abbreviations

CNS:

central nervous system

ECM:

extracellular matrix

ERK:

extracellular signal-regulated kinase

FGF:

fibroblast growth factor

HMEC:

human microvascular endothelial cells

MMP:

matrix metalloproteinase

PI3K:

phosphatidylinositol-3-kinase

PMA:

phorbol myristate acetate

SDS–PAGE:

sodium dodecyl sulfate–polyacrylamide gel electrophoresis

VEGF:

vascular endothelial growth factor

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Acknowledgements

We thank Karen Minter for preparing the manuscript. This work was supported by grants from the American Cancer Society (Illinois Division) to S Mohanam and National Institutes of Health (CA75557, CA85216, CA76350 and CA92393) to JS Rao.

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Authors and Affiliations

  1. Program of Cancer Biology, University of Illinois College of Medicine at Peoria, Box 1649, One Illini Drive, Peoria, 61656, IL, USA

    Niranjan Yanamandra, Krishna V Gumidyala, Jasti S Rao & Sanjeeva Mohanam

  2. Department of Neurosurgery, University of Illinois College of Medicine at Peoria, Peoria, IL, USA

    Kevin G Waldron, William C Olivero, Dzung H Dinh & Jasti S Rao

  3. Department of Pathology, University of Illinois College of Medicine at Peoria, Peoria, IL, USA

    Meena Gujrati

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  1. Niranjan Yanamandra
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Correspondence to Sanjeeva Mohanam.

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Yanamandra, N., Gumidyala, K., Waldron, K. et al. Blockade of cathepsin B expression in human glioblastoma cells is associated with suppression of angiogenesis. Oncogene 23, 2224–2230 (2004). https://doi.org/10.1038/sj.onc.1207338

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