Effect of macrophages on breast cancer cell proliferation, and on expression of hormone receptors, uPAR and HER-2

Lindsten,Therése; Hedbrant,Alexander; Ramberg,Anna; Wijkander,Jonny; Solterbeck,Anja; Eriksson,Margareta; Delbro,Dick; Erlandsson,Ann

doi:10.3892/ijo.2017.3996

Effect of macrophages on breast cancer cell proliferation, and on expression of hormone receptors, uPAR and HER-2

Authors:
- Therése Lindsten
- Alexander Hedbrant
- Anna Ramberg
- Jonny Wijkander
- Anja Solterbeck
- Margareta Eriksson
- Dick Delbro
- Ann Erlandsson
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Affiliations: Department of Clinical Pathology and Cytology, Central Hospital Karlstad, SE-651 88 Karlstad, Sweden, School of Medical Sciences, Örebro University, SE-702 81 Örebro, Sweden, Department of Health Sciences, Karlstad University, SE-651 88 Karlstad, Sweden, Department of Environmental and Life Sciences/Biology, Karlstad University, SE-651 88 Karlstad, Sweden
Published online on: May 11, 2017 https://doi.org/10.3892/ijo.2017.3996
Pages: 104-114
Copyright: © Lindsten et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Malignant tumors, including breast cancers, are frequently infiltrated with innate immune cells and tumor-associated macrophages (TAMs) represent the major inflammatory component in stroma of many tumors. In this study, we examined the immunoreactivity of the macrophage markers CD68 and CD163 as well as the hormone receptors estrogen receptor α (ERα), progesterone receptor (PR), estrogen receptor β1 (ERβ1), human epidermal growth factor receptor 2 (HER-2), matrix metalloproteinase 9 (MMP‑9), urokinase-type plasminogen activator receptor (uPAR) and the proliferations marker Ki67 in 17 breast cancer biopsies. The quantitative score for CD68+ and CD163+ strongly indicate M2 phenotype dominance in the currently investigated biopsies. We found that an increasing level of macrophages was negatively associated with ERα or PR, whereas a positive association was observed for Ki-67 or uPAR. No significant association could be seen between the level of macrophage and HER-2, ERβ1 or MMP-9 expression. Effect of conditioned media (CM) generated from cultured human M1 and M2 macrophage phenotypes were investigated on the proliferation and expression of selected markers in the T47D breast cancer cell line. We found that in contrast to the in vivo situation, in particularly the CM from M1 macrophages decreased the growth and Ki67 expression in T47D, and significantly increased ERβ1 mRNA levels. Moreover, in accordance to the in vivo situation the CM from the macrophages decreased the expression of ERα protein as well as ERα or PR mRNA. In conclusion our results show that macrophages alone have the capability to decrease the tumor cell expression of ERα and PR in vitro. In the tumor environment in vivo macrophages also contribute to an increase in tumor cell expression of uPAR and Ki67, suggesting that macrophages are involved in impairing the prognosis for breast cancer patients.

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