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Beta‐Glucosylceramide Administration (i.p.) Activates Natural Killer T cells In Vivo and Prevents Tumor Metastasis in Mice
Author(s) -
Inafuku Masashi,
Li Changchun,
Kanda Yasuhiro,
Kawamura Toshihiko,
Takeda Kazuyoshi,
Oku Hirosuke,
Watanabe Hisami
Publication year - 2012
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/s11745-012-3666-1
Subject(s) - natural killer t cell , cd1d , metastasis , cancer research , immunotherapy , immunology , in vivo , antigen , biology , medicine , pharmacology , immune system , cancer , cd8 , microbiology and biotechnology
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.