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

Oncogene. 2002 Nov 14;21(52):8011-9. doi: 10.1038/sj.onc.1205894.


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 significantly 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Base Sequence
  • Brain Neoplasms / enzymology
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology
  • Cell Division / genetics*
  • DNA Primers
  • Glioma / enzymology
  • Glioma / genetics*
  • Glioma / pathology
  • Matrix Metalloproteinase 9 / genetics*
  • Mice
  • Neoplasm Invasiveness / genetics*
  • Rats
  • Tumor Cells, Cultured


  • DNA Primers
  • Matrix Metalloproteinase 9