M2 macrophage-derived exosomes promote cell migration and invasion in colon cancer

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 (CRC) metastasis have not been fully characterized. Here we demonstrate that M2 macrophage-regulated CRC 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 CRC cells migration and invasion depended on these two miRNAs. Mechanistically, miR-21-5p and miR-155-5p were transferred to CRC cells by MDE and bound to the BRG1 coding sequence, downregulating expression of BRG1, which has been identified as a key factor promoting CRC metastasis, yet is downregulated in metastatic CRC cells. Collectively, these findings show that M2 macrophages induce CRC 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 CRC cells and M2 macrophages provides a new opportunity for the treatment of metastatic CRC.

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