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Published on: November 28, 2019
MicroRNA-200c Attenuates the Tumor-Infiltrating Capacity of Macrophages
Rebecca Raue1, Ann-Christin Frank1, Dominik C Fuhrmann1
1Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt, Germany.
Abstract:
Macrophages constitute a major part of the tumor-infiltrating immune cells. Within the tumor microenvironment, they acquire an alternatively activated, tumor-supporting phenotype. Factors released by tumor cells are crucial for the recruitment of tumor-associated macrophages. In the present project, we aimed to understand the role of hsa-miR-200c-3p (miR-200c) in the interplay between tumor cells and macrophages. To this end, we employed a coculture system of MCF7 breast tumor cells and primary human macrophages and observed the transfer of miR-200c from apoptotic tumor cells to macrophages, which required intact CD36 receptor in macrophages. We further comprehensively determined miR-200c targets in macrophages by mRNA-sequencing and identified numerous migration-associated mRNAs to be downregulated by miR-200c. Consequently, miR-200c attenuated macrophage infiltration into 3-dimensional tumor spheroids. miR-200c-mediated reduction in infiltration further correlated with a miR-200c migration signature comprised of the four miR-200c-repressed, predicted targets PPM1F, RAB11FIB2, RDX, and MSN.
Insights
MicroRNA-200c (miR-200c) transfers from apoptotic breast tumor cells to macrophages, inhibiting their migration and infiltration into tumors. This transfer, dependent on the CD36 receptor, offers a potential therapeutic target for modulating the tumor microenvironment.
Area of Science:
- Immunology
- Molecular Biology
- Cancer Research
Background:
- Macrophages are key immune cells within the tumor microenvironment, often adopting a tumor-promoting phenotype.
- Tumor-derived factors are critical for recruiting tumor-associated macrophages (TAMs).
- Understanding intercellular communication, particularly microRNA transfer, is vital for cancer progression insights.
Purpose of the Study:
- To investigate the role of hsa-miR-200c-3p (miR-200c) in the interaction between breast tumor cells and macrophages.
- To elucidate the mechanism of miR-200c transfer and its functional consequences on macrophage behavior.
Main Methods:
- Co-culture system using MCF7 breast tumor cells and primary human macrophages.
- Assessment of miR-200c transfer from apoptotic tumor cells to macrophages, investigating the role of the CD36 receptor.
- mRNA sequencing to identify miR-200c targets within macrophages and analysis of macrophage infiltration into 3D tumor spheroids.
Main Results:
- miR-200c was transferred from apoptotic tumor cells to macrophages, a process requiring the CD36 receptor on macrophages.
- miR-200c significantly downregulated numerous migration-associated mRNAs in macrophages.
- This led to attenuated macrophage infiltration into 3-dimensional tumor spheroids, linked to specific repressed targets (PPM1F, RAB11FIB2, RDX, MSN).
Conclusions:
- miR-200c acts as a signaling molecule transferred from tumor cells to macrophages, influencing macrophage function.
- The transfer of miR-200c suppresses macrophage migration, potentially reducing their pro-tumorigenic role in the tumor microenvironment.
- Targeting miR-200c transfer or its downstream effects presents a novel strategy for cancer therapy by modulating TAM infiltration.
