title: Brief Report: Human Mesenchymal Stem-Like Cells Facilitate Floating Tumorigenic Cell Growth via Glutamine-Ammonium Cycle.
abstract: How mesenchymal stem cells (MSCs) promote tumor growth remains incompletely understood. Here, we show that mesenchymal stem-like cells (MSLCs) are commonly present in malignant pleural effusion or ascites of cancer patients, where they directly interact with tumor cells. Chemokines and chemokine receptors, especially the CCL2/CCR2 pathway, are involved in this interaction. As a result, MSLCs exert tumor-promoting effects by enhancing the proliferation and colony formation of tumor-repopulating cells. The underlying molecular basis involves MSLC release of glutamine to tumorigenic cells. Inhibition of glutamine uptake impedes MSC-mediated tumor-promoting effects. More intriguingly, MSLCs take up tumor cell-released ammonium that, in turn, favors MSLC growth. Thus, glutamine and ammonium form a vicious cycle between MSLCs and tumorigenic cells. These findings suggest a potential clinical application by targeting MSLCs in patients with malignant pleural effusions or ascites.
authors.affiliation: State Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Ke
authors.initials: K
authors.lastname: Tang
authors.affiliation: Department of Biochemistry & Molecular Biology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.|Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Liang
authors.initials: L
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Huafeng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry & Molecular Biology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Biochemistry & Molecular Biology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Ruihua
authors.initials: R
authors.lastname: Ma
authors.affiliation: Department of Biochemistry & Molecular Biology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Shunqun
authors.initials: S
authors.lastname: Luo
authors.affiliation: Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Dongbo
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Guoxian
authors.initials: G
authors.lastname: Long
authors.affiliation: Department of Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Mei
authors.initials: M
authors.lastname: Han
authors.affiliation: Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Shunfang
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Anping
authors.initials: A
authors.lastname: Song
authors.affiliation: Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Meizhu
authors.initials: M
authors.lastname: Shen
authors.affiliation: Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China.|Department of Biochemistry & Molecular Biology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Huang
mesh_terms: D064751:Ammonium Compounds / Q000378:metabolism*; D063646:Carcinogenesis / Q000187:drug effects / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology*; D005973:Glutamine / Q000494:pharmacology*; D006801:Humans; D061986:MCF-7 Cells; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D064751:Ammonium Compounds; D005973:Glutamine
keywords: Floating tumorigenic cells; Glutamine/ammonium cycle; Malignant fluids; Mesenchymal stem cells