Loss of CX3CR1 increases accumulation of inflammatory monocytes and promotes gliomagenesis

• DOI: 10.18632/oncotarget.3730
• Publication Date: 2015-09-15T06:31:06Z
• Authors: Xi Feng; Frank Szulzewsky; Alexan Yerevanian; Zhihong Chen; David Heinzmann; Rikke Darling Ras...; Virginia Alvarez-...; Yeonghwan Kim; Bingcheng Wang; Ilaria Tamagno; Hao Zhou; Xiaoxia Li; Helmut Kettenmann; Richard M. Ransohoff; Dolores Hambardzu...
• Keywords: CX3CR1; Monocyte

// Xi Feng 1 , Frank Szulzewsky 2,* Alexan Yerevanian 1,3,* Zhihong Chen David Heinzmann 1,4 Rikke Darling Rasmussen Virginia Alvarez-Garcia Yeonghwan Kim 5 Bingcheng Wang 6 Ilaria Tamagno Hao Zhou 7 Xiaoxia Li Helmut Kettenmann 2 Richard M. Ransohoff 1,8 and Dolores Hambardzumyan Department of Neurosciences at Cleveland Clinic, Cleveland, Ohio, USA Cellular Neurosciences, Max Delbrück Center for Molecular Medicine, Berlin, Germany 3 Case Western Reserve University School 4 Cardiology Tübingen Tübingen, Stem Cell Biology Regenerative Rammelkamp Research, MetroHealth Center, Immunology 8 Neuroinflammation Research * These authors have contributed equally to this work Correspondence to: Hambardzumyan, email: Keywords : CX3CR1/CX3CL1 signaling, glioblastoma, microglia, monocyte Received January 19, 2015 Accepted March 10, Published 30, Abstract The most abundant populations non-neoplastic cells in the glioblastoma (GBM) microenvironment are resident macrophages infiltrating monocytes from blood circulation. mechanisms by which infiltrate into GBM, their fate following infiltration, role GBM growth not known. Here we tested hypothesis that loss fractalkine receptor CX3CR1 microglia would affect gliomagenesis. Deletion Cx3cr1 resulted increased tumor incidence shorter survival times glioma-bearing mice. Loss did accumulation microglia/macrophages peri-tumoral areas, but instead indirectly promoted trafficking CD11b + CD45 hi low Ly-6C Ly-6G - F4/80 -/low circulating inflammatory CNS, resulting perivascular area. Cx3cr1-deficient demonstrated upregulation IL1β expression was inversely proportional gene dosage. Proneural subgroup TCGA patient dataset with high showed compared patients IL1β. cancer stem cell phenotype murine human glioma (GSCs). activated p38 MAPK signaling pathway chemoattractant protein (MCP-1/CCL2) cells. a monocyte-free environment had no impact on alter microglial migration. data suggest enhancing or inhibiting intra-tumoral can be considered as potential strategies decrease tumor-promoting effects GBM.