title: Exosome-Mediated Metastasis: From Epithelial-Mesenchymal Transition to Escape from Immunosurveillance.
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.
authors.affiliation: Cancer Science Institute of Singapore, Centre for Translational Medicine, National University of Singapore, 14 Medical Drive, #12-01, Singapore 117599, Singapore; Department of Haematology-Oncology, National University Cancer Institute, 1E Kent Ridge Road, NUHS Tower Block, Level 7, Singapore 119228, Singapore.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Syn
authors.affiliation: Cancer Science Institute of Singapore, Centre for Translational Medicine, National University of Singapore, 14 Medical Drive, #12-01, Singapore 117599, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore. Electronic address: csiwl@nus.edu.sg.
authors.forename: Lingzhi
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore.
authors.forename: Gautam
authors.initials: G
authors.lastname: Sethi
authors.affiliation: Cancer Science Institute of Singapore, Centre for Translational Medicine, National University of Singapore, 14 Medical Drive, #12-01, Singapore 117599, Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore; UMR 7057 Matter and Complex Systems University Paris Denis Diderot, Paris, France; Comprehensive Cancer Center Institut Gustave Roussy, Villejuif, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Thiery
authors.affiliation: Cancer Science Institute of Singapore, Centre for Translational Medicine, National University of Singapore, 14 Medical Drive, #12-01, Singapore 117599, Singapore; Department of Haematology-Oncology, National University Cancer Institute, 1E Kent Ridge Road, NUHS Tower Block, Level 7, Singapore 119228, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore.
authors.forename: Boon-Cher
authors.initials: BC
authors.lastname: Goh
mesh_terms: D000818:Animals; D058750:Epithelial-Mesenchymal Transition; D055354:Exosomes / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D009362:Neoplasm Metastasis; D019139:Tumor Escape; D059016:Tumor Microenvironment