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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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).
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The authors declare that no conflicts of interest exist.
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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