Adenovirus-mediated expression of antisense MMP-9 in glioma cells inhibits tumor growth and invasion

Sajani S. Lakka, Mannari Rajan, Christopher Gondi, Niranjan Yanamandra, Nirmala Chandrasekar, Sushma L. Jasti, Yoshiaki Adachi, Khawar Siddique, Meena Gujrati, William Olivero, Dzung H. Dinh, Gregory Kouraklis, Athanassios P. Kyritsis, Jasti S. Rao

Research output: Contribution to journalArticle

Abstract

Matrix metalloproteinase 9 (MMP-9) is known to play a major role in cell migration and invasion in both physiological and pathological processes. Our previous work has shown that increased MMP-9 levels are associated with human glioma tumor progression. In this study, we evaluated the ability of an adenovirus containing a 528 bp cDNA sequence in antisense orientation to the 5′ end of the human MMP-9 gene (Ad-MMP-9AS) to inhibit the invasiveness and migratory capacity of the human glioblastoma cell line SBN19 in in vitro and in vivo models. Infection of glioma cells with Ad-MMP-9AS reduced MMP-9 enzyme activity by approximately 90% compared with mock- or Ad-CMV-infected cells. Migration and invasion of glioblastoma cells infected with Ad-MMP-9AS were signicantly inhibited relative to Ad-CMV-infected controls in spheroid and Matrigel assays. Intracranial injections of SNB19 cells infected with Ad-MMP-9AS did not produce tumors in nude mice. However, injecting the Ad-MMP-9AS construct into subcutaneous U87MG tumors in nude mice caused regression of tumor growth. These results support the theory that adenoviral-mediated delivery of the MMP-9 gene in the antisense orientation has therapeutic potential for treating gliomas.

Original languageEnglish (US)
Pages (from-to)8011-8019
Number of pages9
JournalOncogene
Volume21
Issue number52
DOIs
StatePublished - Nov 14 2002

    Fingerprint

Keywords

  • Adenovirus
  • Antisense
  • ECM
  • Glioma
  • MMP-9
  • MT-MMP

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Lakka, S. S., Rajan, M., Gondi, C., Yanamandra, N., Chandrasekar, N., Jasti, S. L., Adachi, Y., Siddique, K., Gujrati, M., Olivero, W., Dinh, D. H., Kouraklis, G., Kyritsis, A. P., & Rao, J. S. (2002). Adenovirus-mediated expression of antisense MMP-9 in glioma cells inhibits tumor growth and invasion. Oncogene, 21(52), 8011-8019. https://doi.org/10.1038/sj.onc.1205894