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| Item Type: | Article |
|---|---|
| Title: | Microglia/macrophage derived human CCL18 promotes glioma progression via CCR8-ACP5 axis analyzed in humanized slice model |
| Creators Name: | Huang, Y. and Motta, E. and Nanvuma, C. and Kuhrt, L.D. and Yuan, Y. and Xia, P. and Lubas, M. and Zhu, S. and Schnauss, M. and Qazi, N. and Hu, F. and Zhang, H. and Lei, T. and Synowitz, M. and Flüh, C. and Kettenmann, H. |
| 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. |
| Keywords: | CCL18, iPSC-Derived Microglia, Glioma, Humanized Glioma Model, Animals, Mice |
| Source: | Cell Reports |
| ISSN: | 2211-1247 |
| Publisher: | Cell Press / Elsevier |
| Volume: | 39 |
| Number: | 2 |
| Page Range: | 110670 |
| Date: | 12 April 2022 |
| Official Publication: | https://doi.org/10.1016/j.celrep.2022.110670 |
| PubMed: | View item in PubMed |
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