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Apoptotictumor cell-derived microRNA-375 uses CD36to alter the tumor-associated macrophage phenotype Ann-ChristinFrank, Stefanie Ebersberger, Annika F. Fink, Sebastian Lampe, Andreas Weigert ,Tobias Schmid, Ingo Ebersberger, Shahzad Nawaz Syed & Bernhard Brüne Nature Communications[IF=12.353] Pub date: 20190308 DOI：10.1038 / s41467-019-08989-2 踏青 春游 Tumor-immune cell interactions shape theimmune cell phenotype, with microRNAs (miRs) beingcrucial components of this crosstalk. How they are transferred and how theyaffect theirtarget landscape, especially in tumor-associated macrophages (TAMs), is largelyunknown. Here wereport that breast cancer cells have a high constitutive expression ofmiR-375, whichis released as a non-exosome entity during apoptosis. Deep sequencingof the miRomepointed to enhanced accumulation of miR-375 in TAMs, facilitated by theuptake oftumor-derived miR-375 via CD36. In macrophages, miR-375 directly targets TNS3and PXN to enhancemacrophage migration and infiltration into tumor spheroids and intumors of axenograft mouse model. In tumor cells, miR-375 regulates CCL2 expressionto increaserecruitment of macrophages. Our study provides evidence for miR transfer fromtumor cells toTAMs and identifies miR-375 as acrucial regulator of phagocyte infiltration and thesubsequent development of a tumor-promoting microenvironment.
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