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The Role of Metastasis‐Associated Protein 1 (MTA1) in Breast Cancer Exosome‐Mediated Intercellular Communication
Author(s) -
Hannafon Bethany N.,
Gaskill Katy,
Calloway Cameron,
Ding WeiQun
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.178.6
Subject(s) - exosome , microvesicles , metastasis , cancer research , tumor microenvironment , biology , breast cancer , flow cytometry , tumor progression , angiogenesis , cancer , microbiology and biotechnology , immunology , microrna , tumor cells , biochemistry , genetics , gene
Background Exosomes are small vesicles that mediate cell‐to‐cell communication and are thought to contribute to tumor progression and metastasis by modifying the tumor microenvironment at both local and distant sites. We recently identified Metastasis‐Associated Protein 1 (MTA1) in exosomes secreted from breast cancer cells, ductal fluids, and breast cancer patient plasma samples. MTA1 is a nuclear co‐regulatory molecule that is highly expressed in many cancers and correlates with tumor metastasis and progression. However, the precise role of MTA1 in breast cancer progression and metastasis is unclear. Objective Our objective was to determine the role of MTA1 in exosome‐mediated signaling in the tumor microenvironment of breast cancer. Methods An antibody array was used to identify MTA1 in breast cancer exosomes. Exosome‐MTA1 expression was confirmed by western blot. tdTomato‐tagged MTA1 expression and transfer were monitored by fluorescent microscopy and flow cytometry. Luciferase reporter constructs were used to monitor gene expression regulation by exosome‐MTA1 transfer. The CRISPR/Cas9 technique was used to knockout MTA1 in breast cancer cells. Endothelial cell tube‐formation assays were performed to ascertain the role of exosome‐MTA1 in angiogenesis. Results MTA1 protein expression was detected in exosomes derived from breast cancer cells, ductal fluids, and breast cancer patient plasma samples. MTA1‐tdTomato expression and exosome‐mediated transfer of MTA1 was observed by fluorescent microscopy and flow cytometry. Importantly, we found that exosome‐MTA1 regulates hypoxia signaling via exosome‐transfer between breast cancer and endothelial cells. Furthermore, exosome‐MTA1 modified the tube formation by endothelial cells. Conclusions This is the first report showing that breast cancer exosomes contain MTA1 and that exosome‐MTA1 alters signaling events in the tumor microenvironment. These observations suggest that exosome‐mediated transfer of MTA1 contributes to breast cancer progression and exosome‐MTA1 may serve as a biomarker and therapeutic target for breast cancer. Support or Funding Information Grant Support: Oklahoma Center for the Advancement of Science and Technology (HR14‐147) and the Oklahoma Shared Clinical and Translational Resources (NIGMS #U54GM104938).