期刊
ONCOTARGET
卷 6, 期 17, 页码 15482-15493出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.3855
关键词
anti-CSF-1; colonization; monocyte-derived cells; microglia; metastasis
资金
- Dres. Bayer-Stiftung (Baden Wurttembergischer Krebspreis, Germany)
- Research Program of the Faculty of Medicine, Georg-August-University Gottingen, Germany
- German Research Council (DFG) in the project of the Forschergruppe 942 [BE 2552/4-1]
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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