Regulation by SHPS-1 of α-GalCer-induced prevention of cancer metastasis (89.14)

Abstract

Abstract [Background] α-GalCer activates NKT cells through the interaction between NKT cells and DCs. SHPS-1 is a transmembrane protein predominantly expressed on DCs. The functional roles of SHPS-1 in the regulation of NKT are investigated by the use of mice bearing mutant SHPS-1, which lack most of its cytoplasmic region. [Methods] B16 melanoma cells were injected into WT or SHPS-1 mutant mice, and α-GalCer or the vehicle was administered. For adoptive transfer of DCs, α-GalCer pulsed DCs were prepared from spleens from WT or SHPS-1 mutant mice, and such cells were injected together with B16 melanoma cells. The mice were sacrificed and the number of tumor colonies in the lung was counted. Splenic or hepatic MNCs were cultured with α-GalCer, and the amounts of IFN-γ and IL-4 in culture supernatants were determined by ELISA. [Results] The prevention of metastasis by α-GalCer was attenuated in the SHPS-1 mutant mice. The antimetastatic effect was induced in WT recipient mice by adoptive transfer of DCs from WT mice, while such effect by that of DCs from SHPS-1 mutant mice was reduced. The production of either INF-γ or IL-4 in response to α-GalCer was reduced in MNCs from SHPS-1 mutant mice. [Conclusion] SHPS-1 on DCs is crucial for the α-GalCer-induced prevention of metastasis and Th1-and Th2-responses by NKT cells.