Investigation of the roles of exosomes in colorectal cancer liver metastasis

Wang,Xia; Ding,Xiaoling; Nan,Lijuan; Wang,Yiting; Wang,Jing; Yan,Zhiqiang; Zhang,Wei; Sun,Jihong; Zhu,Wei; Ni,Bing; Dong,Suzhen; Yu,Lei

doi:10.3892/or.2015.3843

Investigation of the roles of exosomes in colorectal cancer liver metastasis

Authors:
- Xia Wang
- Xiaoling Ding
- Lijuan Nan
- Yiting Wang
- Jing Wang
- Zhiqiang Yan
- Wei Zhang
- Jihong Sun
- Wei Zhu
- Bing Ni
- Suzhen Dong
- Lei Yu
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Affiliations: Institute of Biomedical Engineering and Technology, Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai 200062, P.R. China, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, P.R. China, Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China, School of Life Science, East China Normal University, Shanghai 200241, P.R. China
Published online on: March 9, 2015 https://doi.org/10.3892/or.2015.3843
Pages: 2445-2453

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Abstract

The leading cause of death among cancer patients is tumor metastasis. Tumor-derived exosomes are emerging as mediators of metastasis. In the present study, we demonstrated that exosomes play a pivotal role in the metastatic progression of colorectal cancer. First, a nude mouse model of colorectal cancer liver metastasis was established and characterized. Then, we demonstrated that exosomes from a highly liver metastatic colorectal cancer cell line (HT-29) could significantly increase the metastatic tumor burden and distribution in the mouse liver of Caco-2 colorectal cancer cells, which ordinarily exhibit poor liver metastatic potential. We further investigated the mechanisms by which HT-29-derived-exosomes influence the liver metastasis of colorectal cancer and found that mice treated with HT-29-derived exosomes had a relatively higher level of CXCR4 in the metastatic microenvironment, indicating that exosomes may promote colorectal cancer metastasis by recruiting CXCR4-expressing stromal cells to develop a permissive metastatic microenvironment. Finally, the migration of Caco-2 cells was significantly increased following treatment with HT-29-derived exosomes in vitro, further supporting a role for exosomes in modulating colorectal tumor-derived liver metastasis. The data from the present study may facilitate further translational medicine research into the prevention and treatment of colorectal cancer liver metastasis.

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