Monocytes and macrophages, implications for breast cancer migration and stem cell-like activity and treatment
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Rebecca Ward1, Andrew H. Sims2, Alexander Lee1, Christina Lo1, Luke Wynne1, Humza Yusuf1, Hannah Gregson1, Michael P. Lisanti1, Federica Sotgia1, Göran Landberg1,3 and Rebecca Lamb1
1 Breakthrough Breast Cancer Unit, Institute of Cancer Sciences, Paterson Institute for Cancer Research, University of Manchester, Manchester, UK
2 Applied Bioinformatics of Cancer, University of Edinburgh Cancer Research Centre, Carrington Crescent, Edinburgh, UK
3 Sahlgrenska Cancer Center, University of Gothenburg, Sweden
Rebecca Lamb, email:
Keywords: macrophage, breast, stem-cells, migration
Received: January 20, 2015 Accepted: April 08, 2015 Published: May 19, 2015
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.
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