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Cancer Res. 2016 Dec 1;76(23):6816-6827. Epub 2016 Oct 19.

The Biodistribution and Immune Suppressive Effects of Breast Cancer-Derived Exosomes.

Author information

1
Tumor Microenvironment Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
2
Peter MacCallum Cancer Centre, East Melbourne, and Sir Peter MacCallum Department of Histology, University of Melbourne, Parkville, Australia.
3
Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia.
4
Tumor Microenvironment Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia. andreas.moller@qimrberghofer.edu.au.
5
School of Medicine, University of Queensland, Brisbane, Queensland, Australia.

Abstract

Small membranous secretions from tumor cells, termed exosomes, contribute significantly to intercellular communication and subsequent reprogramming of the tumor microenvironment. Here, we use optical imaging to determine that exogenously administered fluorescently labeled exosomes derived from highly metastatic murine breast cancer cells distributed predominantly to the lung of syngeneic mice, a frequent site of breast cancer metastasis. At the sites of accumulation, exosomes were taken up by CD45+ bone marrow-derived cells. Subsequent long-term conditioning of naïve mice with exosomes from highly metastatic breast cancer cells revealed the accumulation of myeloid-derived suppressor cells in the lung and liver. This favorable immune suppressive microenvironment was capable of promoting metastatic colonization in the lung and liver, an effect not observed from exosomes derived from nonmetastatic cells and liposome control vesicles. Furthermore, we determined that breast cancer exosomes directly suppressed T-cell proliferation and inhibited NK cell cytotoxicity, and hence likely suppressed the anticancer immune response in premetastatic organs. Together, our findings provide novel insight into the tissue-specific outcomes of breast cancer-derived exosome accumulation and their contribution to immune suppression and promotion of metastases. Cancer Res; 76(23); 6816-27.

PMID:
27760789
DOI:
10.1158/0008-5472.CAN-16-0868
[Indexed for MEDLINE]
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