Show simple item record

dc.contributor.authorMartin, F. T.
dc.contributor.authorDwyer, Róisín M.
dc.contributor.authorKelly, J.
dc.contributor.authorKhan, S.
dc.contributor.authorMurphy, J. M.
dc.contributor.authorCurran, C.
dc.contributor.authorMiller, N.
dc.contributor.authorHennessy, E.
dc.contributor.authorDockery, P.
dc.contributor.authorBarry, F. P.
dc.contributor.authorO'Brien, T.
dc.contributor.authorKerin, Michael J.
dc.date.accessioned2019-09-04T11:23:53Z
dc.date.available2019-09-04T11:23:53Z
dc.date.issued2010-01-20
dc.identifier.citationMartin, FT;Dwyer, RM;Kelly, J;Khan, S;Murphy, JM;Curran, C;Miller, N;Hennessy, E;Dockery, P;Barry, FP;O'Brien, T;Kerin, MJ (2010) 'Potential role of mesenchymal stem cells (MSCs) in the breast tumour microenvironment: stimulation of epithelial to mesenchymal transition (EMT)'. Breast Cancer Research And Treatment, 124 :317-326.en_IE
dc.identifier.issn0167-6806
dc.identifier.urihttp://hdl.handle.net/10379/15387
dc.description.abstractBone marrow-derived mesenchymal stem cells (MSCs) are known to specifically migrate to and engraft at tumour sites. Understanding interactions between cancer cells and MSCs has become fundamental to determining whether MSC-tumour interactions should be harnessed for delivery of therapeutic agents or considered a target for intervention. Breast Cancer Cell lines (MDA-MB-231, T47D & SK-Br3) were cultured alone or on a monolayer of MSCs, and retrieved using epithelial specific magnetic beads. Alterations in expression of 90 genes associated with breast tumourigenicity were analysed using low-density array. Expression of markers of epithelial-mesenchymal transition (EMT) and array results were validated using RQ-PCR. Co-cultured cells were analysed for changes in protein expression, growth pattern and morphology. Gene expression and proliferation assays were also performed on indirect co-cultures. Following direct co-culture with MSCs, breast cancer cells expressed elevated levels of oncogenes (NCOA4, FOS), proto-oncogenes (FYN, JUN), genes associated with invasion (MMP11), angiogenesis (VEGF) and anti-apoptosis (IGF1R, BCL2). However, universal downregulation of genes associated with proliferation was observed (Ki67, MYBL2), and reflected in reduced ATP production in response to MSC-secreted factors. Significant upregulation of EMT specific markers (N-cadherin, Vimentin, Twist and Snail) was also observed following co-culture with MSCs, with a reciprocal downregulation in E-cadherin protein expression. These changes were predominantly cell contact mediated and appeared to be MSC specific. Breast cancer cell morphology and growth pattern also altered in response to MSCs. MSCs may promote breast cancer metastasis through facilitation of EMT.en_IE
dc.description.sponsorshipThis study was supported by funding from the National Breast Cancer Research Institute (NBCRI), a Royal College of Surgeons in Ireland (RCSI) Surgical Research Grant (F.T. Martin), a Health Research Board Project Grant (R.M. Dwyer), and a Science Foundation Ireland CSET award (J.M. Murphy, F.P. Barry and T. O’Brien).en_IE
dc.formatapplication/pdfen_IE
dc.language.isoenen_IE
dc.publisherSpringeren_IE
dc.relation.ispartofBreast Cancer Research And Treatmenten
dc.subjectBASAL-LIKE PHENOTYPEen_IE
dc.subjectBONE-MARROWen_IE
dc.subjectVIMENTIN EXPRESSIONen_IE
dc.subjectCANCERen_IE
dc.subjectPROGRESSIONen_IE
dc.subjectMETASTASISen_IE
dc.subjectMIGRATIONen_IE
dc.subjectVEGFen_IE
dc.titlePotential role of mesenchymal stem cells (MSCs) in the breast tumour microenvironment: stimulation of epithelial to mesenchymal transition (EMT)en_IE
dc.typeArticleen_IE
dc.date.updated2019-08-16T10:18:14Z
dc.identifier.doi10.1007/s10549-010-0734-1
dc.local.publishedsourcehttps://doi.org/10.1007/s10549-010-0734-1en_IE
dc.description.peer-reviewedpeer-reviewed
dc.contributor.funderNational Breast Cancer Research Instituteen_IE
dc.contributor.funderHealth Research Boarden_IE
dc.contributor.funderRoyal College of Surgeons in Irelanden_IE
dc.internal.rssid14768020
dc.local.contactRóisín Dwyer, Surgery, Nui Galway. 3008 Email: roisin.dwyer@nuigalway.ie
dc.local.copyrightcheckedYes
dc.local.versionACCEPTED
nui.item.downloads53


Files in this item

Attribution-NonCommercial-NoDerivs 3.0 Ireland
This item is available under the Attribution-NonCommercial-NoDerivs 3.0 Ireland. No item may be reproduced for commercial purposes. Please refer to the publisher's URL where this is made available, or to notes contained in the item itself. Other terms may apply.

The following license files are associated with this item:

Thumbnail

This item appears in the following Collection(s)

Show simple item record