RT Journal Article
T1 Glioma-induced inhibition of caspase-3 in microglia promotes a tumor-supportive phenotype.
A1 Shen, Xianli
A1 Burguillos, Miguel A
A1 Osman, Ahmed M
A1 Frijhoff, Jeroen
A1 Carrillo-Jiménez, Alejandro
A1 Kanatani, Sachie
A1 Augsten, Martin
A1 Saidi, Dalel
A1 Rodhe, Johanna
A1 Kavanagh, Edel
A1 Rongvaux, Anthony
A1 Rraklli, Vilma
A1 Nyman, Ulrika
A1 Holmberg, Johan
A1 Östman, Arne
A1 Flavell, Richard A
A1 Barragan, Antonio
A1 Venero, Jose Luis
A1 Blomgren, Klas
A1 Joseph, Bertrand
AB Glioma cells recruit and exploit microglia (the resident immune cells of the brain) for their proliferation and invasion ability. The underlying molecular mechanism used by glioma cells to transform microglia into a tumor-supporting phenotype has remained elusive. We found that glioma-induced microglia conversion was coupled to a reduction in the basal activity of microglial caspase-3 and increased S-nitrosylation of mitochondria-associated caspase-3 through inhibition of thioredoxin-2 activity, and that inhibition of caspase-3 regulated microglial tumor-supporting function. Furthermore, we identified the activity of nitric oxide synthase 2 (NOS2, also known as iNOS) originating from the glioma cells as a driving stimulus in the control of microglial caspase-3 activity. Repression of glioma NOS2 expression in vivo led to a reduction in both microglia recruitment and tumor expansion, whereas depletion of microglial caspase-3 gene promoted tumor growth. Our results provide evidence that inhibition of the denitrosylation of S-nitrosylated procaspase-3 mediated by the redox protein Trx2 is a part of the microglial pro-tumoral activation pathway initiated by glioma cancer cells.
YR 2016
FD 2016-09-12
LK http://hdl.handle.net/10668/10436
UL http://hdl.handle.net/10668/10436
LA en
DS RISalud
RD Apr 5, 2025