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dc.contributor.authorYao, Qin
dc.contributor.authorQu, Xun
dc.contributor.authorYang, Qifeng
dc.contributor.authorWei, Mingqian
dc.contributor.authorKong, Beihua
dc.date.accessioned2017-05-03T15:52:00Z
dc.date.available2017-05-03T15:52:00Z
dc.date.issued2009
dc.date.modified2010-05-19T06:30:28Z
dc.identifier.issn1021-335X
dc.identifier.urihttp://hdl.handle.net/10072/29730
dc.description.abstractStromal myofibroblasts, activated by crosstalk signaling between the tumour and stroma, play a critical role in tumour development and progression. Chloride intracellular channel 4 (CLIC4) may be functionally import for tumour stromal fibroblast-to-myofibroblast transdifferentiaton, but the molecular mechanism of the process has not been addressed. In this study, the expression of CLIC4 in ovarian cancer tissues was analyzed by immunohistochemistry, and we used an indirect co-culture model of ovarian cancer cells and normal fibroblasts to demonstrate the molecular pathway in which CLIC4 participated during the fibroblast-to-myofibroblast transdifferentiation. The results showed that the expression of CLIC4 in 96.7% of ovarian cancer stroma and correlated with the up-regulation of myofibroblast marker a-SMA. Conditioned medium from ovarian cancer cells (CM) or transforming growth factor-߱ (TGF-߱) increased cellular reactive oxygen species (ROS) levels in fibroblasts, which initiated up-regulation of CLIC4 expression, then resulted in myofibroblast conversion. Moreover, inhibition of CLIC4 significantly reduced the expressions of factors related to the phenotype and functions of myofibroblasts, such as a-SMA, VEGF and HGF. These results suggest that ROS-initiated CLIC4 up-regulation is required for TGF-߱-induced fibroblast-to-myofibroblast transdifferentiaton in ovarian cancer, indicating that inhibiting the CLIC4 might have therapeutic potential targeting tumour stroma.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.format.extent1760452 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglish
dc.language.isoeng
dc.publisherSpandidos Publications
dc.publisher.placeGreece
dc.publisher.urihttp://www.spandidos-publications.com/
dc.publisher.urihttp://www.spandidos-publications.com/or/22/3/541
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom541
dc.relation.ispartofpageto548
dc.relation.ispartofissue3
dc.relation.ispartofjournalOncology Reports
dc.relation.ispartofvolume22
dc.rights.retentionY
dc.subject.fieldofresearchOncology and carcinogenesis
dc.subject.fieldofresearchOncology and carcinogenesis not elsewhere classified
dc.subject.fieldofresearchcode3211
dc.subject.fieldofresearchcode321199
dc.titleCLIC4 mediates TGF-beta1-induced fibroblast-to-myofibroblast transdifferentiation in ovarian cancer
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.facultyGriffith Health, School of Medical Science
gro.rights.copyright© 2009 Spandidos Publications. The attached file is reproduced here in accordance with the copyright policy of the publisher. Please refer to the journal's website for access to the definitive, published version.
gro.date.issued2009
gro.hasfulltextFull Text
gro.griffith.authorWei, Ming Q.


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