Exosomes from BM-MSCs increase the population of CSCs via transfer of miR-142-3p

Bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) are progenitor cells shown to migrate to the tumour and participate in the tumour microenvironment. BM-MSCs play important roles in tumour processes through the release of cytokines or exosomes; however, how BM-MSCs influence the stemness of CSCs in colon cancer cells remains poorly understood.

We isolated exosomes from BM-MSCs and used these exosomes to treat colon cancer cells (HCT-116, HT-29 and SW-480). We compared stemness traits of colon CSCs by cell surface marker (CD133 and Lgr5) and functional assays, such as chemoresistance, colony formation, cell adhesion, invasion and tumour-formation assay. We performed a microRNA array to investigate the differences in exosomal microRNA expression between colon cancer cells, BM-MSCs and co-cultured cells and performed functional and molecular analysis of the gene targets.

In this study, we found that BM-MSC-derived exosomes contained distinct microRNAs, including miR-142-3p, which in turn increased the population of CSCs in colon cancer cells. Depriving miR-142-3p from BM-MSC-derived exosomes clearly decreased the population of colon CSCs. Mechanistically, Numb was found to be the target gene of miR-142-3p, and miR-142-3p promoted the Notch signalling pathway by downregulating Numb.

Our findings indicate that BM-MSC-derived exosomes promote colon cancer stem cell-like traits via miR-142-3p.