Show simple item record

dc.contributor.authorShaker, H
dc.contributor.authorHarrison, H
dc.contributor.authorClarke, Robert B
dc.contributor.authorLandberg, G
dc.contributor.authorBundred, N
dc.contributor.authorVersteeg, H
dc.contributor.authorKirwan, C
dc.date.accessioned2017-06-29T10:36:40Z
dc.date.available2017-06-29T10:36:40Z
dc.date.issued2017-04-18
dc.identifier.citationTissue factor promotes breast cancer stem cell activity in vitro. 2017, 8 (16):25915-25927 Oncotargeten
dc.identifier.issn1949-2553
dc.identifier.pmid28033108
dc.identifier.doi10.18632/oncotarget.13928
dc.identifier.urihttp://hdl.handle.net/10541/620421
dc.description.abstractCancer stem cells (CSCs) are a subpopulation of cells that can self-renew and initiate tumours. The clotting-initiating protein Tissue Factor (TF) promotes metastasis and may be overexpressed in cancer cells with increased CSC activity. We sought to determine whether TF promotes breast CSC activity in vitro using human breast cancer cell lines. TF expression was compared in anoikis-resistant (CSC-enriched) and unselected cells. In cells sorted into of TF-expressing and TF-negative (FACS), and in cells transfected to knockdown TF (siRNA) and overexpress TF (cDNA), CSC activity was compared by (i) mammosphere forming efficiency (MFE) (ii) holoclone colony formation (Hc) and (iii) ALDH1 activity. TF expression was increased in anoikis-resistant and high ALDH1-activity T47D cells compared to unselected cells. FACS sorted TF-expressing T47Ds and TF-overexpressing MCF7s had increased CSC activity compared to TF-low cells. TF siRNA cells (MDAMB231,T47D) had reduced CSC activity compared to control cells. FVIIa increased MFE and ALDH1 in a dose-dependent manner (MDAMB231, T47D). The effects of FVIIa on MFE were abrogated by TF siRNA (T47D). Breast CSCs (in vitro) demonstrate increased activity when selected for high TF expression, when induced to overexpress TF, and when stimulated (with FVIIa). Targeting the TF pathway in vivo may abrogate CSC activity.
dc.language.isoenen
dc.rightsArchived with thanks to Oncotargeten
dc.titleTissue factor promotes breast cancer stem cell activity in vitro.en
dc.typeArticleen
dc.contributor.departmentThe University of Manchester, Manchester Academic Health Science Centre, Department of Academic Surgery, University Hospital of South Manchester, Manchester,en
dc.identifier.journalOncotargeten
refterms.dateFOA2018-12-17T14:56:41Z
html.description.abstractCancer stem cells (CSCs) are a subpopulation of cells that can self-renew and initiate tumours. The clotting-initiating protein Tissue Factor (TF) promotes metastasis and may be overexpressed in cancer cells with increased CSC activity. We sought to determine whether TF promotes breast CSC activity in vitro using human breast cancer cell lines. TF expression was compared in anoikis-resistant (CSC-enriched) and unselected cells. In cells sorted into of TF-expressing and TF-negative (FACS), and in cells transfected to knockdown TF (siRNA) and overexpress TF (cDNA), CSC activity was compared by (i) mammosphere forming efficiency (MFE) (ii) holoclone colony formation (Hc) and (iii) ALDH1 activity. TF expression was increased in anoikis-resistant and high ALDH1-activity T47D cells compared to unselected cells. FACS sorted TF-expressing T47Ds and TF-overexpressing MCF7s had increased CSC activity compared to TF-low cells. TF siRNA cells (MDAMB231,T47D) had reduced CSC activity compared to control cells. FVIIa increased MFE and ALDH1 in a dose-dependent manner (MDAMB231, T47D). The effects of FVIIa on MFE were abrogated by TF siRNA (T47D). Breast CSCs (in vitro) demonstrate increased activity when selected for high TF expression, when induced to overexpress TF, and when stimulated (with FVIIa). Targeting the TF pathway in vivo may abrogate CSC activity.


Files in this item

Thumbnail
Name:
13928-208035-7-PB.pdf
Size:
2.329Mb
Format:
PDF
Description:
Open access full text article

This item appears in the following Collection(s)

Show simple item record