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Title: Tumor microenvironmental cytokines bound to cancer exosomes determine uptake by cytokine receptor-expressing cells and biodistribution.
Austin Authors: Lima, Luize G;Ham, Sunyoung;Shin, Hyunku;Chai, Edna P Z;Lek, Erica S H;Lobb, Richard J;Müller, Alexandra F;Mathivanan, Suresh;Yeo, Belinda ;Choi, Yeonho;Parker, Belinda S;Möller, Andreas
Affiliation: Olivia Newton-John Cancer Research Institute
Department of Bioengineering, Korea University, Seoul, South Korea
Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, Australia
Tumour Microenvironment Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia
Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia
School of Chemistry and Molecular Biosciences, Faculty of Science, University of Queensland, Brisbane, QLD, Australia
Centre for Personalized Nanomedicine, Australian Institute for Bioengineering and Nanotechnology (AIBN), University of Queensland, Brisbane, QLD, Australia
Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC, Australia
Department of Bio-convergence Engineering, Korea University, Seoul, South Korea
School of Biomedical Engineering, Korea University, Seoul, South Korea
Department of Bio-convergence Engineering, Korea University, Seoul, South Korea
Austin Health
Issue Date: 10-Jun-2021
Date: 2021-06-10
Publication information: Nature Communications 2021; 12(1): 3543
Abstract: Metastatic spread of a cancer to secondary sites is a coordinated, non-random process. Cancer cell-secreted vesicles, especially exosomes, have recently been implicated in the guidance of metastatic dissemination, with specific surface composition determining some aspects of organ-specific localization. Nevertheless, whether the tumor microenvironment influences exosome biodistribution has yet to be investigated. Here, we show that microenvironmental cytokines, particularly CCL2, decorate cancer exosomes via binding to surface glycosaminoglycan side chains of proteoglycans, causing exosome accumulation in specific cell subsets and organs. Exosome retention results in changes in the immune landscape within these organs, coupled with a higher metastatic burden. Strikingly, CCL2-decorated exosomes are directed to a subset of cells that express the CCL2 receptor CCR2, demonstrating that exosome-bound cytokines are a crucial determinant of exosome-cell interactions. In addition to the finding that cytokine-conjugated exosomes are detected in the blood of cancer patients, we discovered that healthy subjects derived exosomes are also associated with cytokines. Although displaying a different profile from exosomes isolated from cancer patients, it further indicates that specific combinations of cytokines bound to exosomes could likewise affect other physiological and disease settings.
DOI: 10.1038/s41467-021-23946-8
ORCID: 0000-0001-9548-8843
Journal: Nature Communications
PubMed URL: 34112803
Type: Journal Article
Research Support, Non-U.S. Gov't
Appears in Collections:Journal articles

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