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Nat Commun. 2019 Mar 8;10(1):1135. doi: 10.1038/s41467-019-08989-2.

Apoptotic tumor cell-derived microRNA-375 uses CD36 to alter the tumor-associated macrophage phenotype.

Author information

1
Faculty of Medicine, Institute of Biochemistry I, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany.
2
Institute of Molecular Biology gGmbH, Ackermannweg 4, 55128, Mainz, Germany.
3
Department for Applied Bioinformatics, Institute for Cell Biology and Neuroscience, Goethe-University Frankfurt, Max-von-Laue Strasse 13, 60438, Frankfurt, Germany.
4
Senckenberg Biodiversity and Climate Research Centre Frankfurt (BIK-F), Frankfurt, 60325, Germany.
5
Faculty of Medicine, Institute of Biochemistry I, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany. syed@biochem.uni-frankfurt.de.
6
Faculty of Medicine, Institute of Biochemistry I, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany. b.bruene@biochem.uni-frankfurt.de.
7
German Cancer Research Consortium (DKTK), Partner Site, Frankfurt, 60590, Germany. b.bruene@biochem.uni-frankfurt.de.

Abstract

Tumor-immune cell interactions shape the immune cell phenotype, with microRNAs (miRs) being crucial components of this crosstalk. How they are transferred and how they affect their target landscape, especially in tumor-associated macrophages (TAMs), is largely unknown. Here we report that breast cancer cells have a high constitutive expression of miR-375, which is released as a non-exosome entity during apoptosis. Deep sequencing of the miRome pointed to enhanced accumulation of miR-375 in TAMs, facilitated by the uptake of tumor-derived miR-375 via CD36. In macrophages, miR-375 directly targets TNS3 and PXN to enhance macrophage migration and infiltration into tumor spheroids and in tumors of a xenograft mouse model. In tumor cells, miR-375 regulates CCL2 expression to increase recruitment of macrophages. Our study provides evidence for miR transfer from tumor cells to TAMs and identifies miR-375 as a crucial regulator of phagocyte infiltration and the subsequent development of a tumor-promoting microenvironment.

PMID:
30850595
PMCID:
PMC6408494
DOI:
10.1038/s41467-019-08989-2
[Indexed for MEDLINE]
Free PMC Article

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