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

Eva Rietkötter, Annalen Bleckmann, Michaela Bayerlová, Kerstin Menck, Han Ning Chuang, Britta Wenske, Hila Schwartz, Neta Erez, Claudia Binder, Uwe Karsten Hanisch, Tobias Pukrop*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)15482-15493
Number of pages12
JournalOncotarget
Volume6
Issue number17
DOIs
StatePublished - 2015

Keywords

  • Anti-CSF-1
  • Colonization
  • Metastasis
  • Microglia
  • Monocyte-derived cells

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