title: Anti-CSF-1 treatment is effective to prevent carcinoma invasion induced by monocyte-derived cells but scarcely by microglia.
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.
authors.affiliation: Department of Hematology and Medical Oncology, University Medical Center, 37075 Göttingen, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Rietkötter
authors.affiliation: Department of Hematology and Medical Oncology, University Medical Center, 37075 Göttingen, Germany.
authors.forename: Annalen
authors.initials: A
authors.lastname: Bleckmann
authors.affiliation: Department of Medical Statistics, University Medical Center, 37075 Göttingen, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Bayerlová
authors.affiliation: Department of Hematology and Medical Oncology, University Medical Center, 37075 Göttingen, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Menck
authors.affiliation: Department of Hematology and Medical Oncology, University Medical Center, 37075 Göttingen, Germany.
authors.forename: Han-Ning
authors.initials: HN
authors.lastname: Chuang
authors.affiliation: Department of Hematology and Medical Oncology, University Medical Center, 37075 Göttingen, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Wenske
authors.affiliation: Department of Pathology, Sackler School of Medicine, 69978 Tel Aviv University, Israel.
authors.forename: Hila
authors.initials: H
authors.lastname: Schwartz
authors.affiliation: Department of Pathology, Sackler School of Medicine, 69978 Tel Aviv University, Israel.
authors.forename: Neta
authors.initials: N
authors.lastname: Erez
authors.affiliation: Department of Hematology and Medical Oncology, University Medical Center, 37075 Göttingen, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Binder
authors.affiliation: Institute of Neuropathology, University Medical Center, 37075 Göttingen, Germany.
authors.forename: Uwe-Karsten
authors.initials: UK
authors.lastname: Hanisch
authors.affiliation: Department of Hematology and Medical Oncology, University Medical Center, 37075 Göttingen, Germany.|Department of Hematology and Medical Oncology, University Clinic Regensburg, 93053 Regensburg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Pukrop
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D001921:Brain / Q000166:cytology / Q000276:immunology / Q000473:pathology; D001932:Brain Neoplasms / Q000473:pathology* / Q000556:secondary; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D061986:MCF-7 Cells; D016173:Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D017628:Microglia / Q000166:cytology / Q000276:immunology / Q000473:pathology; D009000:Monocytes / Q000276:immunology; D009361:Neoplasm Invasiveness / Q000276:immunology / Q000473:pathology; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
chemical_list: D000911:Antibodies, Monoclonal; C508586:IL36A protein, human; D007375:Interleukin-1; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor
keywords: anti-CSF-1; colonization; metastasis; microglia; monocyte-derived cells