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Journal Article

Tumor-derived microvesicles mediate human breast cancer invasion through differentially glycosylated EMMPRIN.

MPS-Authors
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Wenzel,  D.
Facility for Electron Microscopy, MPI for biophysical chemistry, Max Planck Society;

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Fulltext (public)

2166613.pdf
(Publisher version), 719KB

Supplementary Material (public)

2166613_Suppl.pdf
(Supplementary material), 2MB

Citation

Menck, K., Scharf, C., Bleckmann, A., Dyck, L., Rost, U., Wenzel, D., et al. (2015). Tumor-derived microvesicles mediate human breast cancer invasion through differentially glycosylated EMMPRIN. Journal of Molecular Cell Biology, 7(2), 143-153. doi:10.1093/jmcb/mju047.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0027-A69F-7
Abstract
Tumor cells secrete not only a variety of soluble factors, but also extracellular vesicles that are known to support the establishment of a favorable tumor niche by influencing the surrounding stroma cells. Here we show that tumor-derived microvesicles (T-MV) also directly influence the tumor cells by enhancing their invasion in a both autologousand heterologous manner. Neither the respective vesicle-free supernatant nor MV from benign mammary cells mediate invasion. Uptake of T-MV is essential for the proinvasive effect. We further identify the highly glycosylated form of the extracellular matrix metalloproteinase inducer (EMMPRIN) as a marker for proinvasive MV. EMMPRIN is also present at high levels on MV from metastatic breast cancer patients in vivo. Anti-EMMPRIN strategies, such as MV deglycosylation, gene knockdown, and specific blocking peptides, inhibit MV-induced invasion. Interestingly, the effect of EMMPRIN-bearing MV is not mediated by matrix metalloproteinases but by activation of the p38/MAPK signaling pathway in the tumor cells. In conclusion, T-MV stimulate cancer cell invasion via a direct feedback mechanism dependent on highly glycosylated EMMPRIN.