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dc.contributor.authorWard, Carol
dc.contributor.authorMeehan, James
dc.contributor.authorMullen, Peter
dc.contributor.authorSupuran, Claudiu
dc.contributor.authorDixon, J. Michael
dc.contributor.authorThomas, Jeremy S.
dc.contributor.authorWinum, Jean-Yves
dc.contributor.authorLambin, Philippe
dc.contributor.authorDubois, Ludwig
dc.contributor.authorPavathaneni, Nanda-Kumar
dc.contributor.authorJarman, Edward J.
dc.contributor.authorRenshaw, Lorna
dc.contributor.authorUm, In Hwa
dc.contributor.authorKay, Charlene
dc.contributor.authorHarrison, David James
dc.contributor.authorKunkler, Ian H.
dc.contributor.authorLangdon, Simon P.
dc.date.accessioned2015-09-02T11:40:08Z
dc.date.available2015-09-02T11:40:08Z
dc.date.issued2015
dc.identifier.citationWard , C , Meehan , J , Mullen , P , Supuran , C , Dixon , J M , Thomas , J S , Winum , J-Y , Lambin , P , Dubois , L , Pavathaneni , N-K , Jarman , E J , Renshaw , L , Um , I H , Kay , C , Harrison , D J , Kunkler , I H & Langdon , S P 2015 , ' Evaluation of carbonic anhydrase IX as a therapeutic target for inhibition of breast cancer invasion and metastasis using a series of in vitro breast cancer models ' Oncotarget , vol. 6 , no. 28 , pp. 24865-24870 .en
dc.identifier.issn1949-2553
dc.identifier.otherPURE: 195547268
dc.identifier.otherPURE UUID: 1d303292-5044-4517-8254-0d6bf516a68b
dc.identifier.urihttp://hdl.handle.net/10023/7393
dc.descriptionThis research was financed in part by a Grant of the 7th Framework Program of the European Union (METOXIA project; HEALTH‐F2‐2009‐222741) and the NGI Pre- Seed grant (NWO n° 93613002).en
dc.description.abstractTriple negative, resistant or metastatic disease are major factors in breast cancer mortality, warranting novel approaches. Carbonic anhydrase IX (CAIX) is implicated in survival, migration and invasion of breast cancer cells and inhibition provides an innovative therapeutic strategy. The efficacy of 5 novel ureido-substituted sulfamate CAIX inhibitors were assessed in increasingly complex breast cancer models, including cell lines in normoxia and hypoxia, 3D spheroids and an ex-vivo explant model utilizing fresh biopsy tissue from different breast cancer subtypes. CAIX expression was evaluated in a tissue microarray (TMA) of 92 paired lymph node and primary breast cancers and 2 inhibitors were appraised in vivo using MDA-MB-231 xenografts. FC11409B, FC9398A, FC9403, FC9396A and S4 decreased cell proliferation and migration and inhibited 3D spheroid invasion. S4, FC9398A and FC9403A inhibited or prevented invasion into collagen. FC9403A significantly reversed established invasion whilst FC9398A and DTP348 reduced xenograft growth. TMA analysis showed increased CAIX expression in triple negative cancers. These data establish CAIX inhibition as a relevant therapeutic goal in breast cancer, targeting the migratory, invasive, and metastatic potential of this disease. The use of biopsy tissue suggests efficacy against breast cancer subtypes, and should provide a useful tool in drug testing against invasive cancers.
dc.format.extent15
dc.language.isoeng
dc.relation.ispartofOncotargeten
dc.rightsCopyright the authors 2015. Licensed under a Creative Commons Attribution 3.0 License http://creativecommons.org/licenses/by/3.0/en
dc.subjectCarbonic anhydrase IXen
dc.subjectBreast canceren
dc.subjectTumour microenvironmenten
dc.subjectInvasionen
dc.subjectHypoxiaen
dc.subjectRC0254 Neoplasms. Tumors. Oncology (including Cancer)en
dc.subjectNDASen
dc.subject.lccRC0254en
dc.titleEvaluation of carbonic anhydrase IX as a therapeutic target for inhibition of breast cancer invasion and metastasis using a series of in vitro breast cancer modelsen
dc.typeJournal articleen
dc.description.versionPostprinten
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Medicineen
dc.description.statusPeer revieweden


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