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

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38 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)78598-78613
Number of pages16
JournalOncotarget
Volume8
Issue number45
DOIs
Publication statusPublished - Jan 1 2017

All Science Journal Classification (ASJC) codes

  • Oncology

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    Takano, Y., Masuda, T., Iinuma, H., Yamaguchi, R., Sato, K., Tobo, T., Hirata, H., Kuroda, Y., Nambara, S., Hayashi, N., Iguchi, T., Ito, S., Eguchi, H., Ochiya, T., Yanaga, K., Miyano, S., & Mimori, K. (2017). Circulating exosomal microRNA-203 is associated with metastasis possibly via inducing tumor-associated macrophages in colorectal cancer. Oncotarget, 8(45), 78598-78613. https://doi.org/10.18632/oncotarget.20009