title: Exosomes derived from SW480 colorectal cancer cells promote cell migration in HepG2 hepatocellular cancer cells via the mitogen-activated protein kinase pathway.
abstract: Exosomes are membrane-derived extracellular vesicles that have recently been recognized as important mediators of intercellular communication. In the present study, we investigated the effects of exosomes derived from SW480 colorectal cancer cells in recipient HepG2 hepatocellular cancer cells. We demonstrated that SW480-derived exosomes were taken up by the recipient HepG2 cells via dynamin-dependent endocytosis and were localized to the HepG2 lysosomes. In addition, SW480-derived exosomes induced the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 following their uptake into HepG2 cells. Of note, these changes occurred during the early phase after exosome treatment. Furthermore, SW480-derived exosomes promoted the migration of recipient HepG2 cells in a wound-healing assay, which was suppressed by pretreatment with U0126, an upstream inhibitor of ERK1/2. These results indicated that SW480-derived exosomes activated a classical mitogen-activated protein kinase pathway in recipient HepG2 cells via dynamin-dependent endocytosis and subsequently enhanced cell migration by ERK1/2 activation. Our results provide new insights into the regulation of cellular functions by exosomes.
authors.affiliation: Department of Biomedical Sciences, Division of Medical Life Sciences, Hirosaki University Graduate School of Health Sciences, Hirosaki, Aomori 036-8564, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Chiba
authors.affiliation: Department of Medical Technology, Hirosaki University School of Health Sciences, Hirosaki, Aomori 036-8564, Japan.
authors.forename: Narumi
authors.initials: N
authors.lastname: Watanabe
authors.affiliation: Department of Medical Technology, Hirosaki University School of Health Sciences, Hirosaki, Aomori 036-8564, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Medical Technology, Hirosaki University School of Health Sciences, Hirosaki, Aomori 036-8564, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Sakamoto
authors.affiliation: Department of Medical Technology, Hirosaki University School of Health Sciences, Hirosaki, Aomori 036-8564, Japan.
authors.forename: Akika
authors.initials: A
authors.lastname: Sato
authors.affiliation: Department of Medical Technology, Hirosaki University School of Health Sciences, Hirosaki, Aomori 036-8564, Japan.
authors.forename: Mizuki
authors.initials: M
authors.lastname: Fujisaki
authors.affiliation: Department of Medical Technology, Hirosaki University School of Health Sciences, Hirosaki, Aomori 036-8564, Japan.
authors.forename: Shiori
authors.initials: S
authors.lastname: Kubota
authors.affiliation: Research Center for Biomedical Sciences, Hirosaki University Graduate School of Health Sciences, Hirosaki, Aomori 036-8564, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Monzen
authors.affiliation: Department of Stress Response Science, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Maruyama
authors.affiliation: Department of Biomedical Sciences, Division of Medical Life Sciences, Hirosaki University Graduate School of Health Sciences, Hirosaki, Aomori 036-8564, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Nanashima
authors.affiliation: Research Center for Biomedical Sciences, Hirosaki University Graduate School of Health Sciences, Hirosaki, Aomori 036-8564, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Kashiwakura
authors.affiliation: Department of Biomedical Sciences, Division of Medical Life Sciences, Hirosaki University Graduate School of Health Sciences, Hirosaki, Aomori 036-8564, Japan.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Nakamura
mesh_terms: D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004705:Endocytosis / Q000235:genetics; D055354:Exosomes / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008247:Lysosomes / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000235:genetics; D010766:Phosphorylation; D015398:Signal Transduction