||
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 both autologous and
heterologous way. Neither the respective vesicle-free supernatant nor MV from benign
mammary cells mediates invasion, suggesting that the 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 pro-invasive 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.
J Mol Cell Biol mju047 first published online December 11, 2014 doi:10.1093/jmcb/mju047
Keywords: breast cancer, microvesicles, invasion, EMMPRIN, glycosylation
This is an Open Access article. READ ME!
Archiver|手机版|科学网 ( 京ICP备07017567号-12 )
GMT+8, 2024-9-27 11:41
Powered by ScienceNet.cn
Copyright © 2007- 中国科学报社