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posted on 2023-03-31, 00:22 authored by Shu Wen Wen, Jaclyn Sceneay, Luize Goncalves Lima, Christina S.F. Wong, Melanie Becker, Sophie Krumeich, Richard J. Lobb, Vanessa Castillo, Ke Ni Wong, Sarah Ellis, Belinda S. Parker, Andreas Möller Representative whole body fluorescent images of C57BL/6 mice at 4, 24 and 48-hours post-intravenous injection of Vybrant® DiD-labeled EO771 exosomes (20 µg; 1.6E11 particles) or liposomes at equivalent particle numbers using the IVIS® Spectrum (PerkinElmer) (n=5/group).
Funding
National Health and Medical Research Council
Cancer Council Queensland
Rio-Tinto-Ride-To-Conquer-Cancer
National Breast Cancer Foundation
ARC
History
ARTICLE 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. ©2016 AACR.
