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

被引：147

作者：

Frank, Ann-Christin ^{[1
]}

Ebersberger, Stefanie ^{[2
]}

Fink, Annika F. ^{[1
]}

Lampe, Sebastian ^{[1
]}

Weigert, Andreas ^{[1
]}

Schmid, Tobias ^{[1
]}

Ebersberger, Ingo ^{[3
,4
]}

Syed, Shahzad Nawaz ^{[1
]}

Bruene, Bernhard ^{[1
,5
]}

机构：

[1] Goethe Univ Frankfurt, Inst Biochem 1, Fac Med, Theodor Stern Kai 7, D-60590 Frankfurt, Germany

[2] Inst Mol Biol gGmbH, Ackermannweg 4, D-55128 Mainz, Germany

[3] Goethe Univ Frankfurt, Inst Cell Biol & Neurosci, Dept Appl Bioinformat, Max von Laue Str 13, D-60438 Frankfurt, Germany

[4] Senckenberg Biodivers & Climate Res Ctr Frankfurt, D-60325 Frankfurt, Germany

[5] German Canc Res Consortium DKTK, Partner Site, D-60590 Frankfurt, Germany

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

关键词：

LOW-DENSITY-LIPOPROTEIN; DOWN-REGULATION; ME SIGNALS; FIND-ME; EXPRESSION; RECEPTOR; PAXILLIN; PROTEIN; IDENTIFICATION; COMMUNICATION;

D O I：

10.1038/s41467-019-08989-2

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页数：18

共 77 条

[1]

Macrophage motility requires distinct α5β1/FAK and α4β1/paxillin signaling events [J].