Exosomes Mediate Stromal Mobilization of Autocrine Wnt-PCP Signaling in Breast Cancer Cell Migration
Open accessAbstract
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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CAFs are a substantial source of growth factors, cytokines and exosomes that can promote tumour growth and modulate therapy responses.
“CAFs are also a substantial source of growth factors, cytokines and exosomes that can promote tumour growth and modulate therapy responses27,106–108.”
From A framework for advancing our understanding of cancer-associated fibroblasts (2020) · cites this paper as [108]
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- Authors
- Luga, V., Zhang, L., Viloria-Petit, A. M., Ogunjimi, A. A., Inanlou, M. R., Chiu, E., Buchanan, M., Hosein, A. N., Basik, M., & Wrana, J. L.
- Affiliations
- Mount Sinai Hospital (CA)
- Jewish General Hospital (CA)
- Corresponding author
- Wrana, Jeffrey L.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2012-12
- Volume
- 151
- Issue
- 7
- Pages
- 1542-1556
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2142755954
- Cited by
- 1,311
- References
- 39
- Citations by year
- 2026: 32 · 2025: 59 · 2024: 95 · 2023: 80 · 2022: 109 · 2021: 123 · 2020: 134 · 2019: 115 · 2018: 103 · 2017: 105 · 2016: 108 · 2015: 106 · 2014: 89 · 2013: 52
- FWCI
- 31.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 385 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Terry Fox Research Institute
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Keywords
- exosomes, Wnt/PCP signaling, breast cancer cell migration, tumor microenvironment, CD81, Wnt11, planar cell polarity, intercellular communication, metastasis, tumor stroma, cell protrusions
- MeSH terms
- Animals, Breast Neoplasms, Cell Movement, Disease Models, Animal, Female, Fibroblasts, Humans, Neoplasm Metastasis, Mice, SCID, Cell Polarity, Autocrine Communication, Cell Line, Tumor, Wnt Proteins, Mice, Exosomes, Tumor Microenvironment, Tetraspanin 28
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