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

Authors: Lakka, SS  Rajan, M  Gondi, C  Yanamandra, N  Chandrasekar, N  Jasti, SL  Adachi, Y  Siddique, K  Gujrati, M  Olivero, W  Dinh, DH  Kouraklis, G  Kyritsis, AP  Rao, JS 
Citation: Lakka SS, etal., Oncogene. 2002 Nov 14;21(52):8011-9.
Pubmed: (View Article at PubMed) PMID:12439751
DOI: Full-text: 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.


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CRRD Object Information
CRRD ID: 8547973
Created: 2014-03-04
Species: All species
Last Modified: 2014-03-04
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.