Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/146973
Title: Hypoxia-induced tumor exosomes promote M2-like macrophage polarization of infiltrating myeloid cells and microRNA-mediated metabolic shift
Authors: Park, Jung Eun
Dutta, Bamaprasad
Tse, Shun Wilford
Gupta, Nikhil
Tan, Chee Fan
Low, Jee Keem
Yeoh, Kheng Wei
Kon, Oi Lian
Tam, James P.
Sze, Siu Kwan
Keywords: Science::Biological sciences
Issue Date: 2019
Source: Park, J. E., Dutta, B., Tse, S. W., Gupta, N., Tan, C. F., Low, J. K., Yeoh, K. W., Kon, O. L., Tam, J. P. & Sze, S. K. (2019). Hypoxia-induced tumor exosomes promote M2-like macrophage polarization of infiltrating myeloid cells and microRNA-mediated metabolic shift. Oncogene, 38(26), 5158-5173. https://dx.doi.org/10.1038/s41388-019-0782-x
Project: MOE2014-T2-2-043
MOE2016- T2-2-018
MOE2016-T3-1-003
NMRC-OF-IRG-0003-2016
Journal: Oncogene
Abstract: Developing tumors rapidly outgrow their oxygen supply and are subject to hypoxia, which stimulates hypersecretion of tumor-derived exosomes that promote angiogenesis, metastasis, and immunosuppression, but the molecular mediators of these pathological effects remain poorly defined. Using quantitative proteomics, we identified that exosomes produced by hypoxic tumor cells are highly enriched in immunomodulatory proteins and chemokines including CSF-1, CCL2, FTH, FTL, and TGFβ. Modeling exosome effects on tumor-infiltrating immune cells, we observed a potent ability of these hypoxia-induced vesicles to influence macrophage recruitment and promote M2-like polarization both in vitro and in vivo. In addition, hypoxic, but not normoxic, tumor exosomes enhanced oxidative phosphorylation in bone marrow-derived macrophages via transfer of let-7a miRNA, resulting in suppression of the insulin-Akt-mTOR signaling pathway. Together, these data demonstrate that hypoxia promotes tumor secretion of biomolecule-loaded exosomes that can modify the immunometabolic profile of infiltrating monocyte-macrophages to better evade host immunity and enhance tumor progression.
URI: https://hdl.handle.net/10356/146973
ISSN: 0950-9232
DOI: 10.1038/s41388-019-0782-x
Rights: © 2019 Springer Nature Limited. All rights reserved.
Fulltext Permission: none
Fulltext Availability: No Fulltext
Appears in Collections:SBS Journal Articles

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