title: Beta-glucosylceramide administration (i.p.) activates natural killer T cells in vivo and prevents tumor metastasis in mice.
abstract: Natural killer (NK) T cells are well known to play important roles in both tumor rejection and the defense against infectious. Therefore, the antitumor potential of NKT cell-activating antigens have been the focus for the development of NKT cell-based immunotherapies. Up to now, several studies have revealed that the administrations of glycolipids (e.g. α-galactosylceramide) can successfully treat certain metastatic tumors. However, liver injuries appeared upon the application of these antigens. We previously examined the potential of using β-glucosylceramide (β-GlcCer) to inhibit tumor metastasis to the liver. The aim of this study was to determine the antimetastatic effects of β-GlcCer and its impact on the activation of NKT cells. Intraperitoneal administration of β-GlcCer enhanced the production of interferon-γ from hepatic lymphocytes containing NKT cells, and increased the cytotoxicity of hepatic lymphocytes against tumor cells. Moreover, β-GlcCer administration suppressed the hepatic metastasis of tumors in wild type (WT) mice, but not in CD1d (-/-) or Jα18 (-/-) mice. The drawback associated with the other glycolipids in liver injury was not noted in WT mice treated with the continuous daily administration of β-GlcCer for 2 weeks. The present study demonstrated that β-GlcCer treatment activates invariant NKT cells, thus resulting in the inhibition of tumor metastasis.
authors.affiliation: Department of Health Sciences, Trans-disciplinary Research Organization for Subtropics and Island Studies, University of the Ryukyus, Senbaru 1, Nishihara, Okinawa 903-0213, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Inafuku
authors.forename: Changchun
authors.initials: C
authors.lastname: Li
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kanda
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Kawamura
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Takeda
authors.forename: Hirosuke
authors.initials: H
authors.lastname: Oku
authors.forename: Hisami
authors.initials: H
authors.lastname: Watanabe
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001219:Aspartate Aminotransferases / Q000097:blood; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D015870:Gene Expression; D005963:Glucosylceramides / Q000008:administration & dosage*; D007155:Immunologic Factors / Q000008:administration & dosage*; D007167:Immunotherapy; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000097:blood / Q000517:prevention & control* / Q000556:secondary; D008223:Lymphoma / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D000099192:CD69 Antigens
chemical_list: D000410:Alanine Transaminase; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000970:Antineoplastic Agents; D001219:Aspartate Aminotransferases; D005963:Glucosylceramides; D007155:Immunologic Factors; D007371:Interferon-gamma; D037181:Lectins, C-Type; D000099192:CD69 Antigens