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Glial cell line‐derived neurotrophic factor increases matrix metallopeptidase 9 and 14 expression in microglia and promotes microglia‐mediated glioma progression

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Item Type:Article
Title:Glial cell line‐derived neurotrophic factor increases matrix metallopeptidase 9 and 14 expression in microglia and promotes microglia‐mediated glioma progression
Creators Name:Huang, Y. and Zhang, B. and Haneke, H. and Haage, V. and Lubas, M. and Yuan, Y. and Xia, P. and Motta, E. and Nanvuma, C. and Dzaye, O. and Hu, F. and Kettenmann, H.
Abstract:Glial cell line‐derived neurotrophic factor (GDNF) is released by glioma cells and promotes tumor growth. We have previously found that GDNF released from the tumor cells is a chemoattractant for microglial cells, the immune cells of the central nervous system. Here we show that GDNF increases matrix metalloproteinase (MMP) 9 and MMP14 expression in cultured microglial cells from mixed sexes of neonatal mice. The GDNF‐induced microglial MMP9 and MMP14 upregulation is mediated by GDNF family receptor alpha 1 receptors and dependent on p38 mitogen‐activated protein kinase signaling. In organotypic brain slices, GDNF promotes the growth of glioma and this effect depends on the presence of microglia. We also previously found that MMP9 and MMP14 upregulation can be mediated by Toll‐like receptor (TLR) 2 signaling and here we demonstrate that GDNF increases the expression of TLR1 and TLR2. In conclusion, GDNF promotes the pro‐tumorigenic phenotype of microglia.
Keywords:GDNF, Glioma, Microglia, MMP9, MMP14, RRID:AB_10013382, RRID:AB_2107448, RRID:AB_2110307, RRID:AB_2111398, RRID:AB_2224402, RRID:AB_2307443, RRID:AB_2336933, RRID:AB_2340476, RRID:AB_2619988, RRID:AB_2687825, RRID:AB_2721181, RRID:AB_330713, RRID:AB_465440, RRID:AB_490936, RRID:AB_657857, RRID:AB_776512, RRID:AB_881233, Animals, Mice
Source:Journal of Neuroscience Research
ISSN:0360-4012
Publisher:Wiley
Volume:99
Number:4
Page Range:1048-1063
Date:April 2021
Official Publication:https://doi.org/10.1002/jnr.24768
PubMed:View item in PubMed

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