TLR4 signal transduction pathways neutralize the effect of Fas signals on glioblastoma cell proliferation and migration.

The Fas pathway is described as an activator of the glioblastoma proliferation by increasing the pathogenicity of this tumour. The lipopolysaccharide (LPS) pathway depending on Toll-like receptor 4 (TLR4) could limit the glioblastoma spreading. Here, Fas and TLR4 pathways were activated in glioblastoma cell lines by an agonist antibody and/or LPS treatment. Activation of the Fas pathway or of the TLR4 pathway induced cell proliferation. However, simultaneous treatment with agonist antibody and LPS decreased proliferation. This anti-proliferative effect was caspase dependent, and a decreased cell migration and matrix metalloproteinase (MMP)-9 expression were also observed. Both TLR4 and MMP-9 were highly expressed in human glioblastoma tissues. These data suggest that TLR4 signal transduction pathways neutralize proliferation and migration induced by Fas pathway activation in glioblastoma cell lines.