期刊
JOURNAL OF IMMUNOLOGY
卷 199, 期 4, 页码 1505-1515出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1700167
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资金
- Japan Society for the Promotion of Science [16J08131]
- Ministry of Education, Science, Sports, and Culture of Japan [24659157]
- Grants-in-Aid for Scientific Research [16J08131, 24659157, 16K10482] Funding Source: KAKEN
Macrophages are polarized into functional classically activated and alternatively activated (M2) phenotypes depending on their microenvironment, and these cells play an important role in the immune system. M2-like polarization of tumor-associated macrophages (TAMs) is activated by various secretions from cancer cells; however, the interaction between cancer cells and TAMs is not well understood. Recent studies showed that cancer cell-derived extracellular vesicles (EVs) contribute to tumor development and modulation of the tumor microenvironment. In the current study, we investigated colorectal cancer-derived EVs containing miR-145 with respect to the polarization of TAMs. Colorectal cancer cells positively secreted miR-145 via EVs, which were taken up by macrophage-like cells. Interestingly, colorectal cancer-derived EVs polarized macrophage-like cells into the M2-like phenotype through the downregulation of histone deacetylase 11. An in vivo study showed that EV-treated macrophages caused significant enlargement of the tumor volumes. These findings suggest that colorectal cancer cells use miR-145 within EVs to efficiently modulate M2-like macrophage polarization and tumor progression.
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