Related Experiment Video
Updated: Sep 27, 2025
Coculture Assays to Study Macrophage and Microglia Stimulation of Glioblastoma Invasion
Published on: October 20, 2016
Microglia/macrophage-derived human CCL18 promotes glioma progression via CCR8-ACP5 axis analyzed in humanized slice
Yimin Huang1, Edyta Motta2, Cynthia Nanvuma3
1Cellular 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.
Abstract:
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.
Insights
Microglia/macrophage-derived CCL18 cytokine promotes glioblastoma growth and invasion. Researchers identified chemokine receptor 8 (CCR8) and acid phosphatase 5 (ACP5) as key signaling components in this process.
Area of Science:
- Neuroscience
- Immunology
- Oncology
Background:
- Glioma-associated microglia/macrophages (GAMs) significantly influence glioblastoma multiforme (GBM) progression.
- CCL18, a cytokine found in human GAMs but not rodent GAMs, is implicated in modulating glioma growth.
Purpose of the Study:
- To investigate the role of CCL18 in promoting glioma growth and invasion.
- To identify the specific receptor and downstream signaling pathways involved in CCL18-mediated glioma progression.
Main Methods:
- Development of a humanized glioma model using induced pluripotent stem cell-derived human microglia and human glioma cells in mouse brain slices.
- Utilizing in vitro, ex vivo, and in vivo GBM models to study CCL18 signaling.
- Identifying the functional receptor for CCL18 on glioma cells and downstream signaling molecules.
Main Results:
- CCL18 significantly enhances glioma cell growth and invasion in the humanized model.
- Chemokine (C-C motif) receptor 8 (CCR8) was identified as the functional receptor for CCL18 on glioma cells.
- Acid phosphatase 5 (ACP5) was revealed as a crucial mediator in the downstream signaling pathway for CCL18-induced glioma growth.
Conclusions:
- Microglia/macrophage-derived CCL18 is a key factor promoting glioma growth.
- The CCL18-CCR8-ACP5 axis represents a potential therapeutic target for GBM treatment.
