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dc.contributor.authorYao, Qin
dc.contributor.authorQu, Xun
dc.contributor.authorYang, Qifeng
dc.contributor.authorGood, David A
dc.contributor.authorDai, Shuzhen
dc.contributor.authorKong, Beihua
dc.contributor.authorWei, Ming Q
dc.date.accessioned2017-05-03T13:02:11Z
dc.date.available2017-05-03T13:02:11Z
dc.date.issued2009
dc.date.modified2009-11-10T05:58:43Z
dc.identifier.issn1476-4598
dc.identifier.doi10.1186/1476-4598-8-78
dc.identifier.urihttp://hdl.handle.net/10072/26564
dc.description.abstractBackground: Tumour stromal myofibroblasts can promote tumour invasion. As these cells are genetically more stable than cancer cells, there has been enormous interest in developing targeted molecular therapies against them. Chloride intracellular channel 4 (CLIC4) and reactive oxygen species (ROS) have been linked with promoting stromal cell transdifferentiation in various cancers, but little is known of their roles in ovarian cancer. In this study, we examined the functional roles that both CLIC4 and ROS play in the process of ovarian cancer cell-stimulated or TGF-߱ induced fibroblast-to-myofibroblast transdifferentiation. We also examine whether it is possible to reverse such a process, with the aim of developing novel therapies against ovarian cancer by targeting activated transdifferentiated myofibroblasts. Results: We demonstrate that TGF-߱ induced or CMSKOV3 activate transdifferentiated myofibroblasts (fibroblasts). These fibroblasts mimic "reactive" stromal myofibroblasts and demonstrate significant up-regulation of CLIC4 expression and increased level of ROS production. Blocking the production of ROS with an antioxidant consequently reduces the expression of CLIC4, and is accompanied by disappearance of a-smooth-muscle actin (a-SMA), a myofibroblast marker, suggesting ROS acts as a signalling molecule that promotes and enhances CLIC4 activities in the myofibroblast transdifferentiaton process. Down-regulation of CLIC4 with a generic agent or specific siRNA both significantly reduces the expression of factors related to the phenotypes and functions of myofibroblasts, such as a-SMA, hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF), thus reversing the myofibroblast phenotype back to fibroblasts. These results convincingly show that ROS and CLIC4 are responsible for TGF-߱ induced fibroblast-to-myofibroblast transdifferentiaton and down-regulation of both is sufficient to block transdifferentiated myofibroblasts. Conclusion: Molecular targeting of ROS and CLIC4 has the potential to develop novel therapies for ovarian cancer.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.format.extent324214 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglish
dc.language.isoeng
dc.publisherBioMed Central Ltd.
dc.publisher.placeUnited Kingdom
dc.publisher.urihttp://www.biomedcentral.com/
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom1
dc.relation.ispartofpageto8
dc.relation.ispartofjournalMolecular Cancer
dc.relation.ispartofvolume8
dc.rights.retentionY
dc.subject.fieldofresearchMedical microbiology not elsewhere classified
dc.subject.fieldofresearchOncology and carcinogenesis
dc.subject.fieldofresearchCancer therapy (excl. chemotherapy and radiation therapy)
dc.subject.fieldofresearchcode320799
dc.subject.fieldofresearchcode3211
dc.subject.fieldofresearchcode321104
dc.titleBlockage of transdifferentiation from fibroblast to myofibroblast in experimental ovarian cancer models
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttp://creativecommons.org/licenses/by/2.0
gro.facultyGriffith Health, School of Medical Science
gro.rights.copyright© 2009 Good, David Andrew et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
gro.date.issued2009
gro.hasfulltextFull Text
gro.griffith.authorWei, Ming Q.


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