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dc.contributor.authorHenke, Alexen
dc.contributor.authorFranco, Omar Een
dc.contributor.authorStewart, Grant Duncanen
dc.contributor.authorRiddick, Antony CPen
dc.contributor.authorKatz, Eladen
dc.contributor.authorHayward, Simon Wen
dc.contributor.authorThomson, Axel Aen
dc.date.accessioned2017-08-15T12:59:12Z
dc.date.available2017-08-15T12:59:12Z
dc.date.issued2016-08-24en
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/266411
dc.description.abstractBACKGROUND: Prostate cancer-associated fibroblasts (CAF) can stimulate malignant progression and invasion of prostatic tumour cells via several mechanisms including those active in extracellular matrix; METHODS: We isolated CAF from prostate cancer patients of Gleason Score 6-10 and confirmed their cancer-promoting activity using an in vivo tumour reconstitution assay comprised of CAF and BPH1 cells. We tested the effects of heat shock protein 90 (HSP90) inhibitors upon reconstituted tumour growth in vivo. Additionally, CAF contractility was measured in a 3D collagen contraction assay and migration was measured by scratch assay; RESULTS: HSP90 inhibitors dipalmitoyl-radicicol and 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) reduced tumour size and proliferation in CAF/BPH1 reconstituted tumours in vivo. We observed that the most contractile CAF were derived from patients with lower Gleason Score and of younger age compared with the least contractile CAF. HSP90 inhibitors radicicol and 17-DMAG inhibited contractility and reduced the migration of CAF in scratch assays. Intracellular levels of HSP70 and HSP90 were upregulated upon treatment with HSP90 inhibitors. Inhibition of HSP90 also led to a specific increase in transforming growth factor beta 2 (TGFβ2) levels in CAF; CONCLUSIONS: We suggest that HSP90 inhibitors act not only upon tumour cells, but also on CAF in the tumour microenvironment.
dc.languageEnglishen
dc.language.isoenen
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectprostate canceren
dc.subjectcancer associated fibroblasten
dc.subjectheat shock proteinen
dc.subjectcontractilityen
dc.titleReduced Contractility and Motility of Prostatic Cancer-Associated Fibroblasts after Inhibition of Heat Shock Protein 90en
dc.typeArticle
dc.description.versionThis is the final version of the article. It first appeared from MDPI via http://dx.doi.org/10.3390/cancers8090077en
prism.number77en
prism.publicationDate2016en
prism.publicationNameCancersen
prism.volume8en
dc.identifier.doi10.17863/CAM.10384
dcterms.dateAccepted2016-08-03en
rioxxterms.versionofrecord10.3390/cancers8090077en
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2016-08-24en
dc.contributor.orcidStewart, Grant Duncan [0000-0003-3188-9140]
rioxxterms.typeJournal Article/Reviewen


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International