作者
Valbona Luga, Liang Zhang, Alicia M Viloria-Petit, Abiodun A Ogunjimi, Mohammad R Inanlou, Elaine Chiu, Marguerite Buchanan, Abdel Nasser Hosein, Mark Basik, Jeffrey L Wrana
发表日期
2012/12/21
期刊
Cell
卷号
151
期号
7
页码范围
1542-1556
出版商
Elsevier
简介
Stroma in the tumor microenvironment plays a critical role in cancer progression, but how it promotes metastasis is poorly understood. Exosomes are small vesicles secreted by many cell types and enable a potent mode of intercellular communication. Here, we report that fibroblast-secreted exosomes promote breast cancer cell (BCC) protrusive activity and motility via Wnt-planar cell polarity (PCP) signaling. We show that exosome-stimulated BCC protrusions display mutually exclusive localization of the core PCP complexes, Fzd-Dvl and Vangl-Pk. In orthotopic mouse models of breast cancer, coinjection of BCCs with fibroblasts dramatically enhances metastasis that is dependent on PCP signaling in BCCs and the exosome component, Cd81 in fibroblasts. Moreover, we demonstrate that trafficking in BCCs promotes tethering of autocrine Wnt11 to fibroblast-derived exosomes. This work reveals an intercellular …
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