Adenovirus-mediated transfer of siRNA against MMP-2 mRNA results in impaired invasion and tumor-induced angiogenesis, induces apoptosis in vitro and inhibits tumor growth in vivo in glioblastoma

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dc.contributor.authorKargiotis, O.en
dc.contributor.authorChetty, C.en
dc.contributor.authorGondi, C. S.en
dc.contributor.authorTsung, A. J.en
dc.contributor.authorDinh, D. H.en
dc.contributor.authorGujrati, M.en
dc.contributor.authorLakka, S. S.en
dc.contributor.authorKyritsis, A. P.en
dc.contributor.authorRao, J. S.en
dc.date.accessioned2015-11-24T19:37:34Z
dc.date.available2015-11-24T19:37:34Z
dc.identifier.issn1476-5594-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/24050
dc.rightsDefault Licence-
dc.subjectAdenoviridae/geneticsen
dc.subjectAnimalsen
dc.subjectApoptosis/*geneticsen
dc.subjectBase Sequenceen
dc.subjectBlotting, Westernen
dc.subjectBrain Neoplasms/blood supply/*pathologyen
dc.subjectCell Line, Tumoren
dc.subjectCell Proliferationen
dc.subjectDNA Primersen
dc.subjectFluorescent Antibody Techniqueen
dc.subjectGlioblastoma/blood supply/*pathologyen
dc.subjectHumansen
dc.subjectMatrix Metalloproteinase 2/*geneticsen
dc.subjectMiceen
dc.subjectMice, Nudeen
dc.subjectNeoplasm Invasiveness/*geneticsen
dc.subjectNeovascularization, Pathologic/*geneticsen
dc.subjectRNA, Messenger/*geneticsen
dc.subjectRNA, Small Interfering/*geneticsen
dc.subject*Transfectionen
dc.titleAdenovirus-mediated transfer of siRNA against MMP-2 mRNA results in impaired invasion and tumor-induced angiogenesis, induces apoptosis in vitro and inhibits tumor growth in vivo in glioblastomaen
heal.abstractInvasive tumors, including gliomas, utilize proteinases to degrade extracellular matrix components and diffuse into the adjacent tissues or migrate toward distant ones. In addition, proteinase activity is required for the formation of new blood vessels within the tumor. Levels of the proteinase matrix metalloproteinase-2 (MMP-2) are highly increased in gliomas. In this study, we examined the effect of the downregulation of MMP-2 via adenovirus-mediated siRNA in gliomas. Here, we show that siRNA delivery significantly decreased levels of MMP-2 in the glioblastoma cell lines U-87 and U-251. U-87 and U-251 cells showed impaired invasion through matrigel as well as decreased migration from tumor spheroids transfected with adenoviral vector expressing siRNA against MMP-2. Additionally, tumor-induced angiogenesis was decreased in in vitro experiments in cultured human microvascular endothelial cells (HMECs) in serum-free conditioned medium of glioblastoma cells transfected with these constructs and co-cultures of glioma cells with HMECs. We also observed decreased angiogenesis in the in vivo dorsal skin-fold chamber model. Moreover, MMP-2 inhibition induced apoptotic cell death in vitro, and suppressed tumor growth of preestablished U-251 intracranial xenografts in nude mice. Thus, specific targeting of MMP-2 may provide a novel, efficient approach for the treatment of gliomas and improve the poor outcomes of patients with these brain tumors.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.primary10.1038/onc.2008.122-
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/18438431-
heal.journalNameOncogeneen
heal.journalTypepeer-reviewed-
heal.languageen-
heal.publicationDate2008-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικήςel
heal.typejournalArticle-
heal.type.elΆρθρο Περιοδικούel
heal.type.enJournal articleen

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