Circulating exosomal microRNA-203 is associated with metastasis possibly via inducing tumor-associated macrophages in colorectal cancer

Yuki Takano, Takaaki Masuda, Hisae Iinuma, Rui Yamaguchi, Kuniaki Sato, Taro Tobo, Hidenari Hirata, Yosuke Kuroda, Sho Nambara, Naoki Hayashi, Tomohiro Iguchi, Shuhei Ito, Hidetoshi Eguchi, Takahiro Ochiya, Katsuhiko Yanaga, Satoru Miyano, Koshi Mimori

研究成果: Contribution to journalArticle査読

63 被引用数 (Scopus)

抄録

A primary tumor can create a premetastatic niche in distant organs to facilitate the development of metastasis. The mechanism by which tumor cells communicate with host cells to develop premetastatic niches is unclear. We focused on the role of microRNA (miR) signaling in promoting metastasis. Here, we identified miR-203 as a signaling molecule between tumors and monocytes in metastatic colorectal cancer (CRC) patients. Notably, high expression of serum exosomal miR-203, a major form in circulation, was associated with distant metastasis and an independent poor prognostic factor, whereas low expression in tumor tissues was a poor prognostic factor in CRC patients. We also found that exosomes carrying miR-203 from CRC cells were incorporated into monocytes and miR-203 could promote the expression of M2 markers in vitro, suggesting miR-203 promoted the differentiation of monocytes to M2-tumor-associated macrophages (TAMs). In a xenograft mouse model, miR-203-transfected CRC cells developed more liver metastasis compared to control cells. In conclusion, serum exosomal miR-203 expression is a novel biomarker for predicting metastasis, possibly via promoting the differentiation of monocytes to M2-TAMs in CRC. Furthermore, we propose the concept of site-dependent functions for miR-203 in tumor progression.

本文言語英語
ページ(範囲)78598-78613
ページ数16
ジャーナルOncotarget
8
45
DOI
出版ステータス出版済み - 2017
外部発表はい

All Science Journal Classification (ASJC) codes

  • 腫瘍学

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