Microglia/macrophage-derived human CCL18 promotes glioma progression via CCR8-ACP5 axis analyzed in humanized slice model.
Autor: | Huang Y; Cellular Neuroscience, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Robert Roessle Strasse 10, 13125 Berlin, Germany; Charité-Universitätsmedizin, 10117 Berlin, Germany; Department of Neurosurgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, 430030 Wuhan, China., Motta E; Cellular Neuroscience, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Robert Roessle Strasse 10, 13125 Berlin, Germany., Nanvuma C; Cellular Neuroscience, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Robert Roessle Strasse 10, 13125 Berlin, Germany; Department of Neurosurgery, University Medical Center Schleswig-Holstein, 24105 Kiel, Germany., Kuhrt LD; Cellular Neuroscience, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Robert Roessle Strasse 10, 13125 Berlin, Germany; Charité-Universitätsmedizin, 10117 Berlin, Germany., Yuan Y; Cellular Neuroscience, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Robert Roessle Strasse 10, 13125 Berlin, Germany., Xia P; Cellular Neuroscience, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Robert Roessle Strasse 10, 13125 Berlin, Germany., Lubas M; Cellular Neuroscience, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Robert Roessle Strasse 10, 13125 Berlin, Germany., Zhu S; Cellular Neuroscience, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Robert Roessle Strasse 10, 13125 Berlin, Germany., Schnauss M; Cellular Neuroscience, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Robert Roessle Strasse 10, 13125 Berlin, Germany., Qazi N; Cellular Neuroscience, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Robert Roessle Strasse 10, 13125 Berlin, Germany., Hu F; Department of Neurosurgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, 430030 Wuhan, China., Zhang H; Department of Neurosurgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, 430030 Wuhan, China., Lei T; Department of Neurosurgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, 430030 Wuhan, China., Synowitz M; Department of Neurosurgery, University Medical Center Schleswig-Holstein, 24105 Kiel, Germany., Flüh C; Cellular Neuroscience, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Robert Roessle Strasse 10, 13125 Berlin, Germany; Department of Neurosurgery, University Medical Center Schleswig-Holstein, 24105 Kiel, Germany. Electronic address: charlotte.flueh@uksh.de., Kettenmann H; Cellular Neuroscience, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Robert Roessle Strasse 10, 13125 Berlin, Germany; Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China. Electronic address: kettenmann@mdc-berlin.de. |
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Jazyk: | angličtina |
Zdroj: | Cell reports [Cell Rep] 2022 Apr 12; Vol. 39 (2), pp. 110670. |
DOI: | 10.1016/j.celrep.2022.110670 |
Abstrakt: | Factors released from glioma-associated microglia/macrophages (GAMs) play a crucial role in glioblastoma multiforme (GBM) progression. Here, we study the importance of CCL18, a cytokine expressed in human but not in rodent GAMs, as a modulator of glioma growth. Since CCL18 signaling could not be studied in classical mouse glioma models, we developed an approach by transplanting induced pluripotent stem cell-derived human microglia and human glioma cells into mouse brain slices depleted of their intrinsic microglia. We observe that CCL18 promotes glioma cell growth and invasion. Chemokine (C-C motif) receptor 8 (CCR8) is identified as a functional receptor for CCL18 on glioma cells, and ACP5 (acid phosphatase 5) is revealed as an important part of the downstream signaling cascade for mediating glioma growth. We conclude, based on the results from an in vitro, ex vivo humanized glioma model and an in vivo GBM model that microglia/macrophage-derived CCL18 promotes glioma growth. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.) |
Databáze: | MEDLINE |
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