Colorectal cancer-derived small extracellular vesicles establish an inflammatory premetastatic niche in liver metastasis. (4th September 2018)

• Record Type: Journal Article
• Authors: Shao, Yingkuan; Chen, Ting; Zheng, Xi; Yang, Sheng; Xu, Kailun; Chen, Xuewen; Xu, Fei; Wang, Lantian; Shen, Yanwei; Wang, Tingyang; Zhang, Mengwen; Hu, Wangxiong; Ye, Chenyang; Yu, XiaoFang; Shao, Jimin; Zheng, Shu
• Is Part Of: Carcinogenesis. Volume 39:Number 11(2018)
• Page Start: 1368
• Page End: 1379
• Publication Date: 2018-09-04
• Subjects: Carcinogenesis -- Periodicals; Cancer -- Genetic aspects -- Periodicals; Cancer -- Prevention -- Periodicals; Cancer -- Periodicals; 616.994071
• DOI: 10.1093/carcin/bgy115
• Languages: English
• ISSNs: 0143-3334

Abstract

Abstract: Liver metastases develop in more than half of the patients with colorectal cancer (CRC) and are associated with a poor prognosis. The factors influencing liver metastasis of CRC are poorly characterized, but this information is urgently needed. We have now discovered that small extracellular vesicles (sEVs; exosomes) derived from CRC can be specifically targeted to liver tissue and induce liver macrophage polarization toward an interleukin-6 (IL-6)-secreting proinflammatory phenotype. More importantly, we found that microRNA-21-5p (miR-21) was highly enriched in CRC-derived sEVs and was essential for creating a liver proinflammatory phenotype and liver metastasis of CRC. Silencing either miR-21 in CRC-sEVs or Toll-like receptor 7 (TLR7) in macrophages, to which miR-21 binds, abolished CRC-sEVs' induction of proinflammatory macrophages. Furthermore, miR-21 expression in plasma-derived sEVs was positively correlated with liver metastasis in CRC patients. Collectively, our data demonstrate a pivotal role of CRC-sEVs in promoting liver metastasis by inducing an inflammatory premetastatic niche through the miR-21–TLR7–IL-6 axis. Thus, sEVs–miR-21 represents a potential prognostic marker and therapeutic target for CRC patients with liver metastasis. Abstract : Colorectal cancer cells induce liver-metastatic tropism via a small extracellular vesicle-mediated crosstalk with inflammatory immune cells.