Shinohara Haruka, Kuranaga Yuki, Kumazaki Minami, Sugito Nobuhiko, Yoshikawa Yuki, Takai Tomoaki, Taniguchi Kohei, Ito Yuko, Akao Yukihiro
United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu 501-1193, Japan;
United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu 501-1193, Japan.
J Immunol. 2017 Aug 15;199(4):1505-1515. doi: 10.4049/jimmunol.1700167. Epub 2017 Jul 10.
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 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.
巨噬细胞根据其微环境被极化为具有功能的经典激活型和替代激活型（M2）表型，这些细胞在免疫系统中发挥重要作用。肿瘤相关巨噬细胞（TAM）的M2样极化由癌细胞的各种分泌物激活；然而，癌细胞与TAM之间的相互作用尚未得到充分了解。最近的研究表明，癌细胞衍生的细胞外囊泡（EV）有助于肿瘤发展和肿瘤微环境的调节。在本研究中，我们研究了含有miR-145的结直肠癌衍生的EV对TAM极化的影响。结直肠癌细胞通过EV阳性分泌miR-145，其被巨噬细胞样细胞摄取。有趣的是，结直肠癌衍生的EV通过下调将巨噬细胞样细胞极化为M2样表型。一项体内研究表明，经EV处理的巨噬细胞导致肿瘤体积显著增大。这些发现表明，结直肠癌细胞利用EV中的miR-145有效调节M2样巨噬细胞极化和肿瘤进展。
