Cytoskeleton-centric protein transportation by exosomes transforms tumor-favorable macrophages

// Zhipeng Chen 1, * , Lijuan Yang 1, * , Yizhi Cui 1 , Yanlong Zhou 1 , Xingfeng Yin 1 , Jiahui Guo 1 , Gong Zhang 1 , Tong Wang 1 , Qing-Yu He 1 1 Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou 510632, China * These authors have contributed equally to this work Correspondence to: Qing-Yu He, email: tqyhe@jnu.edu.cn Tong Wang, email: tongwang@jnu.edu.cn Keywords: exosomes, tumor-associated macrophages, proteome, transportation, cytoskeleton-centric Received: June 16, 2016      Accepted: August 21, 2016      Published: September 1, 2016 ABSTRACT 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.