TY - JOUR
TI - Adenovirus-mediated expression of antisense MMP-9 in glioma cells
inhibits tumor growth and invasion
AU - Lakka, SS
AU - Rajan, M
AU - Gondi, C
AU - Yanamandra, N
AU - Chandrasekar,
AU - N
AU - Jasti, SL
AU - Adachi, Y
AU - Siddique, K
AU - Gujrati, M and
AU - Olivero, W
AU - Dinh, DH
AU - Kouraklis, G
AU - Kyritsis, AP
AU - Rao, JS
JO - Oncogenesis
PY - 2002
VL - 21
TODO - 52
SP - 8011-8019
PB - Nature Publishing Group
SN - 2157-9024
TODO - 10.1038/sj.onc.1205894
TODO - ECM; MMP-9; MT-MMP; adenovirus; antisense; glioma
TODO - 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.
ER -