title: Metabotropic glutamate receptor 3 is involved in B-cell-related tumor apoptosis.
abstract: Cell apoptosis plays a critical role in initiation and progression of tumor and autoimmune diseases, resistance and susceptibility to various therapeutic agents. Our previous study showed that metabotropic glutamate receptor 3 (Grm3) may be involved in autoreactive B-cell apoptosis in a B-cell-depleted agent atacicept-treated lupus-like mice. In the present study, we explore whether Grm3 is involved in the apoptosis in B-cell-related tumor including multiple myeloma and B-cell leukemia. We found that human B-cell leukemia cell line Nalm-6 cells and mouse myeloma cell line SP 2/0 cells could express Grm3. In addition, Grm3 expression emerged mainly in the middle stage of Nalm-6 and SP 2/0 cell apoptosis. Furthermore, apoptosis-induced agents effectively upregulated Grm3 expression in SP 2/0 cells. Critically, Grm3 deficiency promoted tumor progression in an SP 2/0 xenograft mouse model by suppressing cell apoptosis, whereas Grm3 overexpression effectively upregulates SP 2/0 cell apoptosis. Finally, we showed that Grm3 mediated cell apoptosis by Foxo1. Together, our data suggest that Grm3 effectively suppresses the mouse myeloma cell line SP 2/0 cell growth by mediating apoptosis. Thus, Grm3 may be used as an indicator in apoptosis of B-cell-related tumor and a potential target for the treatment of B-cell-related tumor including multiple myeloma and B-cell leukemia.
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, P.R. China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Liu
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, P.R. China.
authors.forename: Zhiding
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, P.R. China.
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Wang
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, P.R. China.
authors.forename: Gaizhi
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, P.R. China.
authors.forename: Gencheng
authors.initials: G
authors.lastname: Han
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, P.R. China.
authors.forename: Guojiang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, P.R. China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Hou
authors.affiliation: College of Pharmacy, Henan University, Kaifeng, Henan 475001, P.R. China.
authors.forename: Tianxiao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, P.R. China.
authors.forename: Beifen
authors.initials: B
authors.lastname: Shen
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Rheumatology, First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Ma
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, P.R. China.
authors.forename: He
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, P.R. China.
authors.forename: Renxi
authors.initials: R
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D005434:Flow Cytometry; D006801:Humans; D015448:Leukemia, B-Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D018094:Receptors, Metabotropic Glutamate; C102718:metabotropic glutamate receptor 3