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

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 <i>miR-203</i> as a signaling molecule between tumors and monocytes in metastatic colorectal cancer (CRC) patients. Notably, high expression of serum exosomal <i>miR-203</i>, 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 <i>miR-203</i> from CRC cells were incorporated into monocytes and <i>miR-203</i> could promote the expression of M2 markers <i>in vitro</i>, suggesting <i>miR-203</i> promoted the differentiation of monocytes to M2-tumor-associated macrophages (TAMs). In a xenograft mouse model, <i>miR-203</i>-transfected CRC cells developed more liver metastasis compared to control cells. In conclusion, serum exosomal <i>miR-203</i> 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 <i>miR-203</i> in tumor progression.