Department of Cell Biology, Key Laboratory of Cell Biology, National Health Commission of the PRC, and Key Laboratory of Medical Cell Biology, Ministry of Education of the PRC, China Medical University, No. 77, Puhe Road, Shenyang North New Area, 110122, Shenyang, Liaoning, China.
Br J Cancer. 2018 Sep;119(6):744-755. doi: 10.1038/s41416-018-0254-z. Epub 2018 Sep 17.
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.
骨髓间充质干细胞（BM-MSCs）是一种祖细胞，已被证明能迁移到肿瘤并参与肿瘤微环境。BM-MSCs 通过释放细胞因子或外泌体在肿瘤过程中发挥重要作用；然而，BM-MSCs 如何影响结肠癌干细胞的干性仍知之甚少。
我们从 BM-MSCs 中分离出外泌体，并使用这些外泌体来处理结肠癌细胞（HCT-116、HT-29 和 SW-480）。我们通过细胞表面标志物（CD133 和 Lgr5）和功能测定（如化疗耐药性、集落形成、细胞黏附、侵袭和肿瘤形成测定）比较结肠 CSCs 的干性特征。我们进行了 microRNA 阵列分析，以研究结肠癌细胞、BM-MSCs 和共培养细胞中外泌体 microRNA 表达的差异，并对基因靶标的功能和分子分析。
在这项研究中，我们发现 BM-MSC 衍生的外泌体包含独特的 microRNAs，包括 miR-142-3p，它反过来增加了结肠癌细胞中 CSCs 的群体。从 BM-MSC 衍生的外泌体中剥夺 miR-142-3p 明显减少了结肠 CSCs 的群体。从机制上讲，发现 Numb 是 miR-142-3p 的靶基因，miR-142-3p 通过下调 Numb 促进了 Notch 信号通路。
我们的研究结果表明，BM-MSC 衍生的外泌体通过 miR-142-3p 促进结肠癌干细胞样特征。
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