uPA/uPAR downregulation inhibits radiation-induced migration, invasion and angiogenesis in IOMM-Lee meningioma cells and decreases tumor growth in vivo

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dc.contributor.authorKargiotis, O.en
dc.contributor.authorChetty, C.en
dc.contributor.authorGogineni, V.en
dc.contributor.authorGondi, C. S.en
dc.contributor.authorPulukuri, S. M.en
dc.contributor.authorKyritsis, A. P.en
dc.contributor.authorGujrati, M.en
dc.contributor.authorKlopfenstein, J. D.en
dc.contributor.authorDinh, D. H.en
dc.contributor.authorRao, J. S.en
dc.date.accessioned2015-11-24T18:58:05Z
dc.date.available2015-11-24T18:58:05Z
dc.identifier.issn1019-6439-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/19243
dc.rightsDefault Licence-
dc.subjectAnimalsen
dc.subjectCapillaries/enzymology/radiation effectsen
dc.subjectCell Line, Tumoren
dc.subjectCell Movement/drug effects/*radiation effectsen
dc.subjectCell Proliferation/drug effects/*radiation effectsen
dc.subjectDown-Regulationen
dc.subjectExtracellular Signal-Regulated MAP Kinases/antagonists & inhibitors/metabolismen
dc.subjectFemaleen
dc.subjectGene Therapy/*methodsen
dc.subjectHumansen
dc.subjectMeningeal Neoplasms/enzymology/pathology/radiotherapy/*therapyen
dc.subjectMeningioma/enzymology/pathology/radiotherapy/*therapyen
dc.subjectMiceen
dc.subjectMice, Nudeen
dc.subjectNeoplasm Invasivenessen
dc.subjectNeovascularization, Pathologic/enzymology/*prevention & controlen
dc.subjectProtein Kinase Inhibitors/pharmacologyen
dc.subject*RNA Interferenceen
dc.subjectRNA, Small Interfering/metabolismen
dc.subjectRadiotherapy/adverse effectsen
dc.subjectReceptor, Epidermal Growth Factor/antagonists & inhibitors/metabolismen
dc.subjectReceptors, Urokinase Plasminogen Activator/genetics/*metabolismen
dc.subjectTransfectionen
dc.subjectUrokinase-Type Plasminogen Activator/genetics/*metabolismen
dc.subjectp38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolismen
dc.titleuPA/uPAR downregulation inhibits radiation-induced migration, invasion and angiogenesis in IOMM-Lee meningioma cells and decreases tumor growth in vivoen
heal.abstractMeningioma is a well-known tumor of the central nervous system, and is treated by surgical resection and/or radiation. Recently, ionizing radiation has been shown to enhance invasiveness of surviving tumor cells, and several proteolytic enzyme molecules, including urokinase plasminogen activator (uPA), seem to be upregulated after radiation. uPA and its receptor (uPAR) have been strongly implicated in tumor invasion, angiogenesis and progression. Hence, the tumor-associated uPA-uPAR system is considered a potential target for cancer therapy. In the present study, we show that radiation increases uPA levels in the IOMM-Lee meningioma cells, and subsequently, increases tumor invasion, migration and angiogenesis in vitro. Studies with signaling molecule inhibitors AG1478, U0126 and SB203580 (specific inhibitors of EGFR, MEK1/2 and p38 respectively) showed inhibition of uPA levels in both basal and irradiated-IOMM-Lee cells. The PI3K inhibitor (LY294002) and the AKT inhibitor (AKT inhibitor IV) also partially decreased uPA expression, whereas SP600125, a JNK inhibitor, did not affect uPA levels in either radiated or non-radiated cells. Further, a bicistronic plasmid construct with small interfering RNA (siRNA) against uPA and its receptor inhibited tumor invasion, migration and angiogenesis in radiation-treated IOMM-Lee cells. In addition, siRNA against uPA and its receptor inhibited subcutaneous tumor growth in athymic nude mice in combination with radiation in a synergistic manner. Thus, the specific targeting of proteases via RNA interference could augment the therapeutic effect of radiation and prevent the adverse effects resulting from tumor cells that receive sublethal doses of radiation within the tumor mass.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/18949356-
heal.journalNameInt J Oncolen
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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