1. Exosomes Mediate Stromal Mobilization of Autocrine Wnt-PCP Signaling in Breast Cancer Cell Migration
- Author
-
Alicia Viloria-Petit, Jeffrey L. Wrana, Abiodun A. Ogunjimi, Marguerite Buchanan, Liang Zhang, Abdel Nasser Hosein, Mohammad R. Inanlou, Elaine Chiu, Valbona Luga, and Mark Basik
- Subjects
Stromal cell ,Breast Neoplasms ,Mice, SCID ,Biology ,Autocrine Communication ,Exosomes ,Exosome ,General Biochemistry, Genetics and Molecular Biology ,Metastasis ,Tetraspanin 28 ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Cell Movement ,Cell Line, Tumor ,medicine ,Tumor Microenvironment ,Animals ,Humans ,Neoplasm Metastasis ,Autocrine signalling ,030304 developmental biology ,0303 health sciences ,Tumor microenvironment ,Biochemistry, Genetics and Molecular Biology(all) ,Wnt signaling pathway ,Cell Polarity ,Fibroblasts ,medicine.disease ,Microvesicles ,3. Good health ,Cell biology ,Wnt Proteins ,Disease Models, Animal ,030220 oncology & carcinogenesis ,Female - Abstract
SummaryStroma 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.
- Published
- 2012
- Full Text
- View/download PDF