Adenovirus-mediated expression of antisense MMP-9 in glioma cells inhibits tumor growth and invasion.
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.
Lakka
Sajani S
SS
Division of Cancer Biology, Department of Biomedical and Therapeutic Sciences, University of Illinois, Peoria 61656, USA.
Rajan
Mannari
M
Gondi
Christopher
C
Yanamandra
Niranjan
N
Chandrasekar
Nirmala
N
Jasti
Sushma L
SL
Adachi
Yoshiaki
Y
Siddique
Khawar
K
Gujrati
Meena
M
Olivero
William
W
Dinh
Dzung H
DH
Kouraklis
Gregory
G
Kyritsis
Athanassios P
AP
Rao
Jasti S
JS
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D002455:Cell Division / Q000235:genetics*; D017931:DNA Primers; D005910:Glioma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D051379:Mice; D009361:Neoplasm Invasiveness / Q000235:genetics*; D051381:Rats; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D020780:Matrix Metalloproteinase 9