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Exosome-Mediated Metastasis: From Epithelial-Mesenchymal Transition to Escape from Immunosurveillance. (Trends Pharmacol Sci, May 2016)

Syn N1, Wang L2, Sethi G3, Thiery JP4, Goh BC5.

Cancer Science Institute of Singapore, National University of Singapore; Department of Haematology-Oncology, National University Cancer Institute
Cancer Science Institute of Singapore, National University of Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore
Cancer Science Institute of Singapore, National University of Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore,; UMR 7057 Matter and Complex Systems University Paris; Comprehensive Cancer Center Institut Gustave Roussy.
Cancer Science Institute of Singapore, National University of Singapore; Department of Haematology-Oncology, National University Cancer Institute; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore

Abstract

Exosomes are extracellular signalosomes that facilitate eukaryotic intercellular communication under a wide range of normal physiological contexts. In malignancies, this regulatory circuit is co-opted to promote cancer cell survival and outgrowth. Tumour-derived exosomes (TDEs) carry a pro-EMT (epithelial-mesenchymal transition) programme including transforming growth factor beta (TGFβ), caveolin-1, hypoxia-inducible factor 1 alpha (HIF1α), and β-catenin that enhances the invasive and migratory capabilities of recipient cells, and contributes to stromal remodelling and premetastatic niche formation. The integrin expression patterns on TDEs appear to dictate their preferential uptake by organ-specific cells, implying a crucial role of this pathway in organotropic metastasis. Through the expression of immunomodulatory molecules such as CD39 and CD73, TDEs modify the immune contexture of the tumour microenvironment, which could have implications for immunotherapy. Hence, targeting TDE dysregulation pathways, such as the heparanase/syndecan-1 axis, could represent novel therapeutic strategies in the quest to conquer cancer.

PMID: 27157716