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    Monocytes and macrophages, implications for breast cancer migration and stem cell-like activity and treatment.

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    Authors
    Ward, Rebecca
    Sims, A
    Lee, Alexander
    Lo, Christina
    Wynne, Luke
    Yusuf, Humza
    Gregson, Hannah J
    Lisanti, Michael P
    Sotgia, Federica
    Landberg, Göran
    Lamb, Rebecca
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    Affiliation
    Breakthrough Breast Cancer Unit, Institute of Cancer Sciences, Paterson Institute for Cancer Research, University of Manchester, Manchester, UK
    Issue Date
    2015-06-10
    
    Metadata
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    Abstract
    Macrophages are a major cellular constituent of the tumour stroma and contribute to breast cancer prognosis. The precise role and treatment strategies to target macrophages remain elusive. As macrophage infiltration is associated with poor prognosis and high grade tumours we used the THP-1 cell line to model monocyte-macrophage differentiation in co-culture with four breast cancer cell lines (MCF7, T47D, MDA-MB-231, MDA-MB-468) to model in vivo cellular interactions. Polarisation into M1 and M2 subtypes was confirmed by specific cell marker expression of ROS and HLA-DR, respectively. Co-culture with all types of macrophage increased migration of ER-positive breast cancer cell lines, while M2-macrophages increased mammosphere formation, compared to M1-macrophages, in all breast cancer cells lines. Treatment of cells with Zoledronate in co-culture reduced the "pro-tumourigenic" effects (increased mammospheres/migration) exerted by macrophages. Direct treatment of breast cancer cells in homotypic culture was unable to reduce migration or mammosphere formation.Macrophages promote "pro-tumourigenic" cellular characteristics of breast cancer cell migration and stem cell activity. Zoledronate targets macrophages within the microenvironment which in turn, reduces the "pro-tumourigenic" characteristics of breast cancer cells. Zoledronate offers an exciting new treatment strategy for both primary and metastatic breast cancer.
    Citation
    Monocytes and macrophages, implications for breast cancer migration and stem cell-like activity and treatment. 2015, 6 (16):14687-99 Oncotarget
    Journal
    Oncotarget
    URI
    http://hdl.handle.net/10541/559320
    PubMed ID
    26008983
    Type
    Article
    Language
    en
    ISSN
    1949-2553
    Collections
    All Paterson Institute for Cancer Research

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