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Exosomes from human adipose-derived mesenchymal stem cells promote migration through Wnt signaling pathway in a breast cancer cell model

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Abstract

Human mesenchymal stem cell (MSC)-conditioned medium (CM) was previously reported to affect the biology of tumor cells; however, the precise mechanisms remain unclear. Here, we show that MSCs secreted 40–100 nm particles, which have the typical characteristics of exosomes, and these MSC-derived exosomes promoted migration of the breast cancer cell line MCF7. Global gene expression profiling revealed that several cancer-related signaling pathways were upregulated after exosome treatment in MCF7, and the Wnt signaling pathway was further confirmed to be activated. Our findings demonstrated a new mechanism through which MSC-CM may contribute to tumor cell migration.

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References

  1. Liechty KW, MacKenzie TC, Shaaban AF, Radu A, Moseley AM, Deans R, Marshak DR, Flake AW (2000) Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep. Nat Med 6(11):1282–1286

    Article  PubMed  CAS  Google Scholar 

  2. Karnoub AE, Dash AB, Vo AP, Sullivan A, Brooks MW, Bell GW, Richardson AL, Polyak K, Tubo R, Weinberg RA (2007) Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature 449(7162):557–563

    Article  PubMed  CAS  Google Scholar 

  3. De Boeck A, Pauwels P, Hensen K, Rummens JL, Westbroek W, Hendrix A, Maynard D, Denys H, Lambein K, Braems G, Gespach C, Bracke M, Wever OD (2013) Bone marrow-derived mesenchymal stem cells promote colorectal cancer progression through paracrine neuregulin 1/HER3 signalling. Gut 62(4):550–560

    Google Scholar 

  4. Schorey JS, Bhatnagar S (2008) Exosome function: from tumor immunology to pathogen biology. Traffic 9(6):871–881

    Article  PubMed  CAS  Google Scholar 

  5. Peinado H, Aleckovic M, Lavotshkin S, Matei I, Costa-Silva B, Moreno-Bueno G, Hergueta-Redondo M, Williams C, Garcia-Santos G, Ghajar C, Nitadori-Hoshino A, Hoffman C, Badal K, Garcia BA, Callahan MK, Yuan J, Martins VR, Skog J, Kaplan RN, Brady MS, Wolchok JD, Chapman PB, Kang Y, Bromberg J, Lyden D (2012) Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat Med 18(6):883–891

    Article  PubMed  CAS  Google Scholar 

  6. Simons M, Raposo G (2009) Exosomes–vesicular carriers for intercellular communication. Curr Opin Cell Biol 21(4):575–581

    Article  PubMed  CAS  Google Scholar 

  7. Li T, Yan Y, Wang B, Qian H, Zhang X, Shen L, Wang M, Zhou Y, Zhu W, Li W, Xu W (2013) Exosomes derived from human umbilical cord mesenchymal stem cells alleviate liver fibrosis. Stem Cells Dev 22(6):845–854

    Google Scholar 

  8. Lai RC, Arslan F, Lee MM, Sze NS, Choo A, Chen TS, Salto-Tellez M, Timmers L, Lee CN, El Oakley RM, Pasterkamp G, de Kleijn DP, Lim SK (2010) Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. Stem Cell Res 4(3):214–222

    Article  PubMed  CAS  Google Scholar 

  9. Cao Y, Sun Z, Liao L, Meng Y, Han Q, Zhao RC (2005) Human adipose tissue-derived stem cells differentiate into endothelial cells in vitro and improve postnatal neovascularization in vivo. Biochem Biophys Res Commun 332(2):370–379

    Article  PubMed  CAS  Google Scholar 

  10. Ohshima K, Inoue K, Fujiwara A, Hatakeyama K, Kanto K, Watanabe Y, Muramatsu K, Fukuda Y, Ogura S, Yamaguchi K, Mochizuki T (2010) Let-7 microRNA family is selectively secreted into the extracellular environment via exosomes in a metastatic gastric cancer cell line. PLoS One 5(10):e13247

    Article  PubMed  Google Scholar 

  11. Hood JL, Pan H, Lanza GM, Wickline SA (2009) Paracrine induction of endothelium by tumor exosomes. Lab Invest 89(11):1317–1328

    Article  PubMed  Google Scholar 

  12. Nasser MW, Qamri Z, Deol YS, Smith D, Shilo K, Zou X, Ganju RK (2011) Crosstalk between chemokine receptor CXCR4 and cannabinoid receptor CB2 in modulating breast cancer growth and invasion. PLoS One 6(9):e23901

    Article  PubMed  CAS  Google Scholar 

  13. Lustig B, Behrens J (2003) The Wnt signaling pathway and its role in tumor development. J Cancer Res Clin Oncol 129(4):199–221

    PubMed  CAS  Google Scholar 

  14. Brabletz T, Hlubek F, Spaderna S, Schmalhofer O, Hiendlmeyer E, Jung A, Kirchner T (2005) Invasion and metastasis in colorectal cancer: epithelial-mesenchymal transition, mesenchymal-epithelial transition, stem cells and beta-catenin. Cells Tissues Organs 179(1–2):56–65

    Article  PubMed  CAS  Google Scholar 

  15. Khakoo AY, Pati S, Anderson SA, Reid W, Elshal MF, Rovira II, Nguyen AT, Malide D, Combs CA, Hall G, Zhang J, Raffeld M, Rogers TB, Stetler-Stevenson W, Frank JA, Reitz M, Finkel T (2006) Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi’s sarcoma. J Exp Med 203(5):1235–1247

    Article  PubMed  CAS  Google Scholar 

  16. Djouad F, Plence P, Bony C, Tropel P, Apparailly F, Sany J, Noel D, Jorgensen C (2003) Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals. Blood 102(10):3837–3844

    Article  PubMed  CAS  Google Scholar 

  17. Roorda BD, Elst A, Boer TG, Kamps WA, de Bont ES (2010) Mesenchymal stem cells contribute to tumor cell proliferation by direct cell–cell contact interactions. Cancer Invest 28(5):526–534

    Article  PubMed  CAS  Google Scholar 

  18. Camussi G, Deregibus MC, Bruno S, Cantaluppi V, Biancone L (2010) Exosomes/microvesicles as a mechanism of cell-to-cell communication. Kidney Int 78(9):838–848

    Article  PubMed  CAS  Google Scholar 

  19. Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9(6):654–659

    Article  PubMed  CAS  Google Scholar 

  20. Giles RH, van Es JH, Clevers H (2003) Caught up in a Wnt storm: Wnt signaling in cancer. Biochim Biophys Acta 1653(1):1–24

    PubMed  CAS  Google Scholar 

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Acknowledgments

This study was supported by grants from National Natural Science Foundation of China (No. 30830052, 30700321, and 30800429) and Program for Cheung Kong Scholars and Innovative Research Team in University-PCSIRT (No. IRT0909).

Conflict of interest

The authors declare that no conflicts of interest exist.

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Corresponding author

Correspondence to Robert Chunhua Zhao.

Additional information

Ruizhu Lin and Shihua Wang have contributed equally to this study.

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Fig. 1

Migration capacity of MCF7 was reduced in MSC culture medium without exosome. MCF7 pretreated with original MSC culture medium and the MSC culture medium without exosome for 24 h and were then subjected to (A) wound repair assays. The wound was generated at time 0 h and cell migration into the wound was analyzed by phase-contrast microscopy at 18 h. One of 3 independent experiments is shown here: (B) modified Boyden chamber assays. The number of cells that migrated to the bottom of the insert membrane was quantified after staining with crystal violet. Representative images are shown at top. Graphs in the bottom indicate the average number of cells demonstrated as absorbance at the bottom of the insert membrane (TIFF 4407 kb)

Fig. 2

Gene ontology analysis of (A) genes associated with epithelial cell migration (GO0010631) or (B) genes associated with cell migration (GO0016477) (TIFF 2577 kb)

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Lin, R., Wang, S. & Zhao, R.C. Exosomes from human adipose-derived mesenchymal stem cells promote migration through Wnt signaling pathway in a breast cancer cell model. Mol Cell Biochem 383, 13–20 (2013). https://doi.org/10.1007/s11010-013-1746-z

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  • DOI: https://doi.org/10.1007/s11010-013-1746-z

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