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    Tissue factor promotes breast cancer stem cell activity in vitro.

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    Authors
    Shaker, H
    Harrison, H
    Clarke, Robert B
    Landberg, G
    Bundred, N
    Versteeg, H
    Kirwan, C
    Affiliation
    The University of Manchester, Manchester Academic Health Science Centre, Department of Academic Surgery, University Hospital of South Manchester, Manchester,
    Issue Date
    2017-04-18
    
    Metadata
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    Abstract
    Cancer 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.
    Citation
    Tissue factor promotes breast cancer stem cell activity in vitro. 2017, 8 (16):25915-25927 Oncotarget
    Journal
    Oncotarget
    URI
    http://hdl.handle.net/10541/620421
    DOI
    10.18632/oncotarget.13928
    PubMed ID
    28033108
    Type
    Article
    Language
    en
    ISSN
    1949-2553
    ae974a485f413a2113503eed53cd6c53
    10.18632/oncotarget.13928
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

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