Anti-CSF-1 treatment is effective to prevent carcinoma invasion induced by monocyte-derived cells but scarcely by microglia
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Eva Rietkötter1, Annalen Bleckmann1, Michaela Bayerlová2, Kerstin Menck1, Han-Ning Chuang1, Britta Wenske1, Hila Schwartz3, Neta Erez3, Claudia Binder1, Uwe-Karsten Hanisch4, Tobias Pukrop1,5
1Department of Hematology and Medical Oncology, University Medical Center, 37075 Göttingen, Germany
2Department of Medical Statistics, University Medical Center, 37075 Göttingen, Germany
3Department of Pathology, Sackler School of Medicine, 69978 Tel Aviv University, Israel
4Institute of Neuropathology, University Medical Center, 37075 Göttingen, Germany
5Department of Hematology and Medical Oncology, University Clinic Regensburg, 93053 Regensburg, Germany
Tobias Pukrop, e-mail: [email protected]
Keywords: anti-CSF-1, colonization, monocyte-derived cells, microglia, metastasis
Received: January 5, 2015 Accepted: April 29, 2015 Published: May 12, 2015
The mononuclear phagocytic system is categorized in three major groups: monocyte-derived cells (MCs), dendritic cells and resident macrophages. During breast cancer progression the colony stimulating factor 1 (CSF-1) can reprogram MCs into tumor-promoting macrophages in the primary tumor. However, the effect of CSF-1 during colonization of the brain parenchyma is largely unknown.
Thus, we analyzed the outcome of anti-CSF-1 treatment on the resident macrophage population of the brain, the microglia, in comparison to MCs, alone and in different in vitro co-culture models. Our results underline the addiction of MCs to CSF-1 while surprisingly, microglia were not affected. Furthermore, in contrast to the brain, the bone marrow did not express the alternative ligand, IL-34. Yet treatment with IL-34 and co-culture with carcinoma cells partially rescued the anti-CSF-1 effects on MCs. Further, MC-induced invasion was significantly reduced by anti-CSF-1 treatment while microglia-induced invasion was reduced to a lower extend. Moreover, analysis of lung and breast cancer brain metastasis revealed significant differences of CSF-1 and CSF-1R expression.
Taken together, our findings demonstrate not only differences of anti-CSF-1 treatment on MCs and microglia but also in the CSF-1 receptor and ligand expression in brain and bone marrow as well as in brain metastasis.
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