title: Effective internalization of U251-MG-secreted exosomes into cancer cells and characterization of their lipid components.
abstract: Exosomes, the natural vehicles of various biological molecules, have been examined in several research fields including drug delivery. Although understanding of the biological functions of exosomes has increased, how exosomes are transported between cells remains unclear. We hypothesized that cell tropism is important for effective exosomal intercellular communication and that parental cells regulate exosome movement by modulating constituent exosomal molecules. Herein, we demonstrated the strong translocation of glioblastoma-derived exosomes (U251exo) into their parental (U251) cells, breast cancer (MDA-MB-231) cells, and fibrosarcoma (HT-1080). Furthermore, disruption of proteins of U251exo by enzymatic treatment did not affect their uptake. Therefore, we focused on lipid molecules of U251exo with the expectation that they are crucial for effective incorporation of U251exo by cancer cells. Phosphatidylethanolamine was identified as a unique lipid component of U251-MG cell-derived extracellular vesicles. From these results, valuable insight is provided into the targeting of U251exo to cancer cells, which will help to develop a cancer-targeted drug delivery system.
authors.affiliation: Department of Medicinal Chemistry, Misasagi-Shichono-cho 1, Yamashina-ku, Kyoto-shi, Kyoto 607-8412, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Toda
authors.affiliation: Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Misasagi-Nakauchi-cho 5, Yamashina-ku, Kyoto-shi, Kyoto 607-8414, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Takata
authors.affiliation: Department of Medicinal Chemistry, Misasagi-Shichono-cho 1, Yamashina-ku, Kyoto-shi, Kyoto 607-8412, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nakagawa
authors.affiliation: Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Misasagi-Nakauchi-cho 5, Yamashina-ku, Kyoto-shi, Kyoto 607-8414, Japan.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Kawakami
authors.affiliation: Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Misasagi-Nakauchi-cho 5, Yamashina-ku, Kyoto-shi, Kyoto 607-8414, Japan.
authors.forename: Shusuke
authors.initials: S
authors.lastname: Fujioka
authors.affiliation: Department of Medicinal Chemistry, Misasagi-Shichono-cho 1, Yamashina-ku, Kyoto-shi, Kyoto 607-8412, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Department of Medicinal Chemistry, Misasagi-Shichono-cho 1, Yamashina-ku, Kyoto-shi, Kyoto 607-8412, Japan.
authors.forename: Yasunao
authors.initials: Y
authors.lastname: Hattori
authors.affiliation: Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Misasagi-Nakauchi-cho 5, Yamashina-ku, Kyoto-shi, Kyoto 607-8414, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kitamura
authors.affiliation: Department of Medicinal Chemistry, Misasagi-Shichono-cho 1, Yamashina-ku, Kyoto-shi, Kyoto 607-8412, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Akaji
authors.affiliation: Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Misasagi-Nakauchi-cho 5, Yamashina-ku, Kyoto-shi, Kyoto 607-8414, Japan. Electronic address: ash@mb.kyoto-phu.ac.jp.
authors.forename: Eishi
authors.initials: E
authors.lastname: Ashihara
mesh_terms: D002450:Cell Communication; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D055354:Exosomes / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000378:metabolism*; D010714:Phosphatidylethanolamines / Q000032:analysis*
chemical_list: D010714:Phosphatidylethanolamines; C483858:phosphatidylethanolamine
keywords: Cancer cell targeting; Drug delivery system; Exosomes; Glioblastoma; Lipid