Anti-CSF-1 treatment is effective to prevent carcinoma invasion induced by monocyte-derived cells but scarcely by microglia

Abstract

// Eva Rietkötter 1 , Annalen Bleckmann 1 , Michaela Bayerlová 2 , Kerstin Menck 1 , Han-Ning Chuang 1 , Britta Wenske 1 , Hila Schwartz 3 , Neta Erez 3 , Claudia Binder 1 , Uwe-Karsten Hanisch 4 , Tobias Pukrop 1, 5 1 Department of Hematology and Medical Oncology, University Medical Center, 37075 Göttingen, Germany 2 Department of Medical Statistics, University Medical Center, 37075 Göttingen, Germany 3 Department of Pathology, Sackler School of Medicine, 69978 Tel Aviv University, Israel 4 Institute of Neuropathology, University Medical Center, 37075 Göttingen, Germany 5 Department of Hematology and Medical Oncology, University Clinic Regensburg, 93053 Regensburg, Germany Correspondence to: Tobias Pukrop, e-mail: tobias.pukrop@ukr.de Keywords: anti-CSF-1, colonization, monocyte-derived cells, microglia, metastasis Received: January 5, 2015      Accepted: April 29, 2015      Published: May 12, 2015 ABSTRACT 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.