title: Isopentenyl pyrophosphate secreted from Zoledronate-stimulated myeloma cells, activates the chemotaxis of γδT cells.
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.
authors.affiliation: Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Kyoto, Japan; Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto, Japan. Electronic address: ash@mb.kyoto-phu.ac.jp.
authors.forename: Eishi
authors.initials: E
authors.lastname: Ashihara
authors.affiliation: Technology Research Laboratory, Shimadzu Corporation, Kyoto, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Munaka
authors.affiliation: Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Kimura
authors.affiliation: Department of Bio-analytical Chemistry, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Nakagawa
authors.affiliation: Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nakagawa
authors.affiliation: Technology Research Laboratory, Shimadzu Corporation, Kyoto, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kanai
authors.affiliation: Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Hideyo
authors.initials: H
authors.lastname: Hirai
authors.affiliation: Technology Research Laboratory, Shimadzu Corporation, Kyoto, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Abe
authors.affiliation: Department of Clinical Laboratory Medicine, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Miida
authors.affiliation: Department of Bio-analytical Chemistry, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Yamato
authors.affiliation: Department of Electronic and Photonic Systems, Waseda University, Tokyo, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Shoji
authors.affiliation: Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Taira
authors.initials: T
authors.lastname: Maekawa
mesh_terms: D045744:Cell Line, Tumor; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D017077:Culture Media, Conditioned; D004164:Diphosphonates / Q000494:pharmacology*; D045782:Hemiterpenes / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D000077211:Zoledronic Acid
chemical_list: D017077:Culture Media, Conditioned; D004164:Diphosphonates; D045782:Hemiterpenes; D007093:Imidazoles; D009943:Organophosphorus Compounds; D016692:Receptors, Antigen, T-Cell, gamma-delta; C004809:isopentenyl pyrophosphate; D000077211:Zoledronic Acid
keywords: Chemotaxis; Isopentenyl pyrophosphate; Multiple myeloma; Tumor immunity; γδT cells