Journal
ONCOTARGET
Volume 7, Issue 41, Pages 67387-67402Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.11794
Keywords
exosomes; tumor-associated macrophages; proteome; transportation; cytoskeleton-centric
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Funding
- National Basic Research Program 973 of China [2014CBA02000, 2011CB910700]
- International Collaboration Program [2014DFB30010]
- Guangdong Natural Science Foundation [32213027/32215077, 2014A030313369]
- Key Special Project on the Integration of Industry, Education and Research of Guangzhou [201604020002]
- Key Program of Applied Science and Technology of Guangdong Province
- Postdoctoral Science Foundation of China [2015M570752]
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The exosome is a key initiator of pre-metastatic niche in numerous cancers, where macrophages serve as primary inducers of tumor microenvironment. However, the proteome that can be exosomally transported from cancer cells to macrophages has not been sufficiently characterized so far. Here, we used colorectal cancer (CRC) exosomes to educate tumor-favorable macrophages. With a SILAC-based mass spectrometry strategy, we successfully traced the proteome transported from CRC exosomes to macrophages. Such a proteome primarily focused on promoting cytoskeleton rearrangement, which was biologically validated with multiple cell lines. We reproduced the exosomal transportation of functional vimentin as a proof-of-concept example. In addition, we found that some CRC exosomes could be recognized by macrophages via Fc receptors. Therefore, we revealed the active and necessary role of exosomes secreted from CRC cells to transform cancer-favorable macrophages, with the cytoskeleton-centric proteins serving as the top functional unit.
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