Article | Published:

Cellular and Molecular Biology

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

British Journal of Cancervolume 119pages744755 (2018) | Download Citation

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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

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Acknowledgements

This work was supported by Grants (Nos. 31371424, 31571457) from the National Natural Science Foundation of China and Basic Research Project of Education Department of Liaoning Province (LZ2015071) and Ministry of Education of the PRC (IRT13101).

Author information

Affiliations

  1. 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

    • Hongdan Li
    •  & Feng Li

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Contributions

HD. L.: Conceived the idea, designed and carried out the experiments, and drafted the manuscript; F.L.: conceived the idea, supervised the project, and helped in finalising the manuscript.

Ethics approval and consent to participate

The study was conducted in compliance with the provisions of the Declaration of Helsinki. All the experimental procedures were approved by the Institutional Animal Care and Use Committee of the China Medical University (IACUC Issue No.14061) in accordance with guidelines set forth by the university for animal research. The final protocol and amendments were reviewed and approved by the independent ethics committee of the China Medical University. All patients provided informed consent prior to undergoing screening procedures.

Competing interests

The authors declare no competing interests.

Availability of data and materials

The datasets used and analysed during the current study are available from the corresponding author on reasonable request.

Note

This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).

Corresponding author

Correspondence to Feng Li.

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DOI

https://doi.org/10.1038/s41416-018-0254-z