title: Adenovirus-mediated expression of antisense MMP-9 in glioma cells inhibits tumor growth and invasion.
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 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.
authors.affiliation: Division of Cancer Biology, Department of Biomedical and Therapeutic Sciences, University of Illinois, Peoria 61656, USA.
authors.forename: Sajani S
authors.initials: SS
authors.lastname: Lakka
authors.forename: Mannari
authors.initials: M
authors.lastname: Rajan
authors.forename: Christopher
authors.initials: C
authors.lastname: Gondi
authors.forename: Niranjan
authors.initials: N
authors.lastname: Yanamandra
authors.forename: Nirmala
authors.initials: N
authors.lastname: Chandrasekar
authors.forename: Sushma L
authors.initials: SL
authors.lastname: Jasti
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Adachi
authors.forename: Khawar
authors.initials: K
authors.lastname: Siddique
authors.forename: Meena
authors.initials: M
authors.lastname: Gujrati
authors.forename: William
authors.initials: W
authors.lastname: Olivero
authors.forename: Dzung H
authors.initials: DH
authors.lastname: Dinh
authors.forename: Gregory
authors.initials: G
authors.lastname: Kouraklis
authors.forename: Athanassios P
authors.initials: AP
authors.lastname: Kyritsis
authors.forename: Jasti S
authors.initials: JS
authors.lastname: Rao
mesh_terms: 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
chemical_list: D017931:DNA Primers; D020780:Matrix Metalloproteinase 9