title: Investigation of the roles of exosomes in colorectal cancer liver metastasis.
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.
authors.affiliation: Institute of Biomedical Engineering and Technology, Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai 200062, P.R. China.
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Biomedical Engineering and Technology, Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai 200062, P.R. China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Ding
authors.affiliation: Institute of Biomedical Engineering and Technology, Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai 200062, P.R. China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Nan
authors.affiliation: Institute of Biomedical Engineering and Technology, Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai 200062, P.R. China.
authors.forename: Yiting
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute of Biomedical Engineering and Technology, Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai 200062, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Institute of Biomedical Engineering and Technology, Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai 200062, P.R. China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Yan
authors.affiliation: Institute of Biomedical Engineering and Technology, Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai 200062, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, P.R. China.
authors.forename: Jihong
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.affiliation: School of Life Science, East China Normal University, Shanghai 200241, P.R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Ni
authors.affiliation: Institute of Biomedical Engineering and Technology, Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai 200062, P.R. China.
authors.forename: Suzhen
authors.initials: S
authors.lastname: Dong
authors.affiliation: Institute of Biomedical Engineering and Technology, Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai 200062, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yu
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D055354:Exosomes / Q000378:metabolism / Q000473:pathology*; D019073:HT29 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000556:secondary*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000473:pathology*; D019718:Receptors, CXCR4 / Q000378:metabolism; D059016:Tumor Microenvironment / Q000502:physiology
chemical_list: D019718:Receptors, CXCR4