Molecular definition of the pro-tumorigenic phenotype of glioma-activated microglia.

摘要: Microglia are myeloid cells residing in the central nervous system that participate inflammatory responses and could promote injury repair. Gliomas attract microglia polarize them into tumor-supporting matrix remodeling, invasion, angiogenesis, suppression of adaptive immunity. Although signaling pathways critical regulators underlying classical inflammation well established, signal transduction transcriptional circuits alternative activation poorly known. Using primary rat microglial cultures exposed to glioma conditioned medium or lipopolysaccharide (LPS), we demonstrate adapt different fates pro-inflammatory alternatively activated cells. Glioma-derived factors increased cell motility, phagocytosis, sustained proliferation was mediated by enhanced focal adhesion kinase PI-3K/Akt signaling. The signals from induced ERK p38 MAPK but not JNK failed activate Stat1 NFκB Transcriptome analysis at 6 h after exposure glioma-conditioned LPS revealed patterns gene expression. Glioma-induced associated with induction genes coding for ID (inhibitor DNA binding) 1/3 c-Myc, markers phenotype Arg1, MT1-MMP, CXCL14, numerous cytokines/chemokines implicated immune trafficking. Many inflammation-related be induced. Our study indicates first time molecular direct toward pro-invasive, immunosuppressive phenotype.