M2 Macrophage-Derived Exosomes Promote Cell Migration and Invasion in Colon Cancer
M2 Macrophage-Derived Exosomes Promote Cell Migration and Invasion in Colon Cancer
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M2巨噬细胞衍生的外泌体促进结肠癌细胞迁移和侵袭
DOI：
10.1158/0008-5472.can-18-0014
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发表时间：
2019-01-01
期刊：
影响因子：
11.2
通讯作者：
Wang, Guihua
中科院分区：
文献类型：
--
作者：
Lan, Jingqin;Sun, Li;Wang, Guihua
临床和实验证据表明，肿瘤相关巨噬细胞促进癌症的发生和发展。然而，巨噬细胞衍生的调节结直肠癌转移的分子决定因素尚未得到充分表征。在这里，我们证明了M2巨噬细胞调节的结直肠癌细胞的迁移和侵袭依赖于M2巨噬细胞衍生的外泌体（MDE）。MDE中miR-21-5p和miR-155-5p高表达，MDE介导的结直肠癌细胞的迁移和侵袭依赖于这两种mirna。机制上，miR-21-5p和miR-155-5p通过MDE转移到结直肠癌细胞中，与BRG1编码序列结合，下调BRG1的表达，而BRG1是促进结直肠癌转移的关键因子，但在转移性结直肠癌细胞中下调。综上所述，这些研究结果表明，M2巨噬细胞诱导结直肠癌细胞的迁移和侵袭，并在恶性进展过程中对肿瘤微环境的响应中提供了显著的BRG1表达可塑性。这种结直肠癌细胞与M2巨噬细胞之间动态、互惠的相互作用，为转移性结直肠癌的治疗提供了新的契机。意义：这些发现报道了来自M2巨噬细胞的含有mirna的外泌体在调节结直肠癌细胞的迁移和侵袭中的功能作用。
Clinical and experimental evidence has shown that tumor-associated macrophages promote cancer initiation and progression. However, the macrophage-derived molecular determinants that regulate colorectal cancer metastasis have not been fully characterized. Here, we demonstrate that M2 macrophage-regulated colorectal cancer cells' migration and invasion is dependent upon M2 macrophage-derived exosomes (MDE). MDE displayed a high expression level of miR-21-5p and miR-155-5p, and MDE-mediated colorectal cancer cells' migration and invasion depended on these two miRNAs. Mechanistically, miR-21-5p and miR-155-5p were transferred to colorectal cancer cells by MDE and bound to the BRG1 coding sequence, downregulating expression of BRG1, which has been identified as a key factor promoting the colorectal cancer metastasis, yet is downregulated in metastatic colorectal cancer cells. Collectively, these findings show that M2 macrophages induce colorectal cancer cells' migration and invasion and provide significant plasticity of BRG1 expression in response to tumor microenvironments during malignant progression. This dynamic and reciprocal cross-talk between colorectal cancer cells and M2 macrophages provides a new opportunity for the treatment of metastatic colorectal cancer.Significance: These findings report a functional role for miRNA-containing exosomes derived from M2 macrophages in regulating migration and invasion of colorectal cancer cells.