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.
Highlights
Breast cancer is the most common disease in women in the Western world with an incidence rate of 600,000 and a mortality rate of 200,000 each year [1]
To confirm that macrophage infiltration is associated with poor prognosis in primary breast cancer, we analysed the expression of CD68 protein within a tissue microarray
We have identified increased macrophage infiltration within Luminal B and ERBB2 subtypes, and demonstrated that macrophage infiltration is associated with tumour recurrence, high grade and positive lymph node status which is consistent with previous published literature [16,17,18,19]
Summary
Breast cancer is the most common disease in women in the Western world with an incidence rate of 600,000 and a mortality rate of 200,000 each year [1]. Breast cancer diagnosis and treatment has significantly improved in recent years with increased disease-free survival in breast cancer patients. Despite these improvements, a significant proportion of breast cancers are either resistant to treatment or show disease recurrence [2, 3]. Recurrences at metastatic sites represent a major cause of mortality in breast cancer patients [6, 7]. Resistance to therapy impedes the improvement of breast cancer mortality rates within the clinic. Research suggests that cancer stem cells (CSCs) play an important role in breast www.impactjournals.com/oncotarget cancer and therapy resistance [8] emphasising the need for new treatment strategies [9, 10]. CSCs can be identified by various cellular markers including CD44+/CD24- and ALDH1 expression, or by their ability to form mammospheres [13,14,15]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
