@article{3082614, title = "Adenovirus-mediated expression of antisense MMP-9 in glioma cells inhibits tumor growth and invasion", author = "Lakka, SS and Rajan, M and Gondi, C and Yanamandra, N and Chandrasekar, and N and Jasti, SL and Adachi, Y and Siddique, K and Gujrati, M and and Olivero, W and Dinh, DH and Kouraklis, G and Kyritsis, AP and Rao, JS", journal = "Oncogenesis", year = "2002", volume = "21", number = "52", pages = "8011-8019", publisher = "Nature Publishing Group", issn = "2157-9024", doi = "10.1038/sj.onc.1205894", keywords = "ECM; MMP-9; MT-MMP; adenovirus; antisense; glioma", 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." }