Exosomes Mediate Stromal Mobilization of Autocrine Wnt-PCP Signaling in Breast Cancer Cell Migration | Zendy

Valbona Luga | Zendy; Liang Zhang | Zendy; Alicia ViloriaPetit | Zendy; Abiodun A. Ogunjimi | Zendy; Mohammad Reza Inanlou | Zendy; Elaine Chiu | Zendy; Marguerite Buchanan | Zendy; Abdel Hosein | Zendy; Mark Basik | Zendy; Jeffrey L. Wrana | Zendy

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Exosomes Mediate Stromal Mobilization of Autocrine Wnt-PCP Signaling in Breast Cancer Cell Migration

Author(s) -

Valbona Luga,

Liang Zhang,

Alicia ViloriaPetit,

Abiodun A. Ogunjimi,

Mohammad Reza Inanlou,

Elaine Chiu,

Marguerite Buchanan,

Abdel Hosein,

Mark Basik,

Jeffrey L. Wrana

Publication year - 2012

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2012.11.024

Subject(s) - autocrine signalling , microvesicles , biology , wnt signaling pathway , microbiology and biotechnology , exosome , stromal cell , cancer research , cell signaling , cancer associated fibroblasts , tumor microenvironment , signal transduction , cell migration , cancer cell , fibroblast , cell , cancer , cell culture , microrna , biochemistry , genetics , tumor cells , gene

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 communication pathway whereby fibroblast exosomes mobilize autocrine Wnt-PCP signaling to drive BCC invasive behavior.

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