Isopentenyl pyrophosphate secreted from Zoledronate-stimulated myeloma cells, activates the chemotaxis of γδT cells

Eishi Ashihara, Tatsuya Munaka, Shinya Kimura, Saori Nakagawa, Yoko Nakagawa, Masaki Kanai, Hideyo Hirai, Hirohisa Abe, Takashi Miida, Susumu Yamato, Shuichi Shoji, Taira Maekawa

    Research output: Contribution to journalArticle

    5 Citations (Scopus)

    Abstract

    γδT cell receptor (TCR)-positive T cells, which control the innate immune system, display anti-tumor immunity as well as other non-immune-mediated anti-cancer effects. γδT cells expanded ex vivo by nitrogen-containing bisphosphonate (N-BP) treatment can kill tumor cells. N-BP inhibits farnesyl pyrophosphate synthase in the mevalonate pathway, resulting in the accumulation of isopentenyl pyrophosphate (IPP), which is a stimulatory antigen for γδT cells. We have previously observed that as they get closer, migrating γδT cells increase in speed toward target multiple myeloma (MM) cells. In the present study, we investigated the γδT cell chemotactic factors involving using a micro total analysis system-based microfluidic cellular analysis device. The addition of supernatant from RPMI8226 MM cells treated with the N-BP zoledronic acid (ZOL) or the addition of IPP to the device induced chemotaxis of γδT cells and increased the speed of migration compared to controls. Analysis of the ZOL-treated RPMI8226 cell supernatant revealed that it contained IPP secreted in a ZOL-dose-dependent manner. These observations indicate that IPP activates the chemotaxis of γδT cells toward target MM cells treated with ZOL.

    Original languageEnglish
    Pages (from-to)650-655
    Number of pages6
    JournalBiochemical and Biophysical Research Communications
    Volume463
    Issue number4
    DOIs
    Publication statusPublished - 2015 May 11

    Fingerprint

    zoledronic acid
    T-cells
    Chemotaxis
    T-Lymphocytes
    Diphosphonates
    Multiple Myeloma
    Nitrogen
    Tumors
    TCF Transcription Factors
    Microfluidic Analytical Techniques
    Equipment and Supplies
    Neoplasms
    Mevalonic Acid
    Chemotactic Factors
    T-Cell Antigen Receptor
    Immune system
    isopentenyl pyrophosphate
    Immune System
    Immunity
    Microfluidics

    Keywords

    • Chemotaxis
    • Isopentenyl pyrophosphate
    • Multiple myeloma
    • Tumor immunity
    • γδT cells

    ASJC Scopus subject areas

    • Biochemistry
    • Biophysics
    • Cell Biology
    • Molecular Biology

    Cite this

    Isopentenyl pyrophosphate secreted from Zoledronate-stimulated myeloma cells, activates the chemotaxis of γδT cells. / Ashihara, Eishi; Munaka, Tatsuya; Kimura, Shinya; Nakagawa, Saori; Nakagawa, Yoko; Kanai, Masaki; Hirai, Hideyo; Abe, Hirohisa; Miida, Takashi; Yamato, Susumu; Shoji, Shuichi; Maekawa, Taira.

    In: Biochemical and Biophysical Research Communications, Vol. 463, No. 4, 11.05.2015, p. 650-655.

    Research output: Contribution to journalArticle

    Ashihara, E, Munaka, T, Kimura, S, Nakagawa, S, Nakagawa, Y, Kanai, M, Hirai, H, Abe, H, Miida, T, Yamato, S, Shoji, S & Maekawa, T 2015, 'Isopentenyl pyrophosphate secreted from Zoledronate-stimulated myeloma cells, activates the chemotaxis of γδT cells', Biochemical and Biophysical Research Communications, vol. 463, no. 4, pp. 650-655. https://doi.org/10.1016/j.bbrc.2015.05.118
    Ashihara, Eishi ; Munaka, Tatsuya ; Kimura, Shinya ; Nakagawa, Saori ; Nakagawa, Yoko ; Kanai, Masaki ; Hirai, Hideyo ; Abe, Hirohisa ; Miida, Takashi ; Yamato, Susumu ; Shoji, Shuichi ; Maekawa, Taira. / Isopentenyl pyrophosphate secreted from Zoledronate-stimulated myeloma cells, activates the chemotaxis of γδT cells. In: Biochemical and Biophysical Research Communications. 2015 ; Vol. 463, No. 4. pp. 650-655.
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    abstract = "γδT cell receptor (TCR)-positive T cells, which control the innate immune system, display anti-tumor immunity as well as other non-immune-mediated anti-cancer effects. γδT cells expanded ex vivo by nitrogen-containing bisphosphonate (N-BP) treatment can kill tumor cells. N-BP inhibits farnesyl pyrophosphate synthase in the mevalonate pathway, resulting in the accumulation of isopentenyl pyrophosphate (IPP), which is a stimulatory antigen for γδT cells. We have previously observed that as they get closer, migrating γδT cells increase in speed toward target multiple myeloma (MM) cells. In the present study, we investigated the γδT cell chemotactic factors involving using a micro total analysis system-based microfluidic cellular analysis device. The addition of supernatant from RPMI8226 MM cells treated with the N-BP zoledronic acid (ZOL) or the addition of IPP to the device induced chemotaxis of γδT cells and increased the speed of migration compared to controls. Analysis of the ZOL-treated RPMI8226 cell supernatant revealed that it contained IPP secreted in a ZOL-dose-dependent manner. These observations indicate that IPP activates the chemotaxis of γδT cells toward target MM cells treated with ZOL.",
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    AU - Nakagawa, Saori

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    AU - Kanai, Masaki

    AU - Hirai, Hideyo

    AU - Abe, Hirohisa

    AU - Miida, Takashi

    AU - Yamato, Susumu

    AU - Shoji, Shuichi

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