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

• Published in: Oncotarget Vol. 6; no. 17; pp. 15482 - 15493
• Main Authors: Rietkötter, Eva, Bleckmann, Annalen, Bayerlová, Michaela, Menck, Kerstin, Chuang, Han-Ning, Wenske, Britta, Schwartz, Hila, Erez, Neta, Binder, Claudia, Hanisch, Uwe-Karsten, Pukrop, Tobias
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 20-06-2015
• Subjects: Animals; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacology; Brain - cytology; Brain - immunology; Brain - pathology; Brain Neoplasms - pathology; Brain Neoplasms - secondary; Breast Neoplasms - immunology; Breast Neoplasms - pathology; Cell Line, Tumor; Cell Movement; Cell Proliferation; Female; Humans; Interleukin-1 - pharmacology; Macrophage Colony-Stimulating Factor - antagonists & inhibitors; Macrophage Colony-Stimulating Factor - biosynthesis; Macrophage Colony-Stimulating Factor - immunology; Macrophages - immunology; MCF-7 Cells; Mice; Mice, Inbred BALB C; Microglia - cytology; Microglia - immunology; Microglia - pathology; Monocytes - immunology; Neoplasm Invasiveness - immunology; Neoplasm Invasiveness - pathology; Receptor, Macrophage Colony-Stimulating Factor - antagonists & inhibitors; Receptor, Macrophage Colony-Stimulating Factor - biosynthesis; Research Paper; monocyte-derived cells; anti-CSF-1; colonization; metastasis; microglia
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.3855

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.