Glial cell line-derived neurotrophic factor increases matrix metallopeptidase 9 and 14 expression in microglia and promotes microglia-mediated glioma progression.
Yimin HuangBaole ZhangHannah HanekeVerena HaageMalgorzata LubasYang YuanPengfei XiaEdyta MottaCynthia NanvumaOmar DzayeFeng HuHelmut KettenmannPublished in: Journal of neuroscience research (2021)
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.
Keyphrases
- inflammatory response
- toll like receptor
- neuropathic pain
- poor prognosis
- lipopolysaccharide induced
- lps induced
- nuclear factor
- cell migration
- immune response
- long non coding rna
- type diabetes
- induced apoptosis
- endothelial cells
- metabolic syndrome
- cell proliferation
- tyrosine kinase
- multiple sclerosis
- cerebrospinal fluid
- diabetic rats
- protein kinase
- anti inflammatory
- oxidative stress