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Reduced microglial CX3CR1 expression delays neurofibromatosis‐1 glioma formation
Author(s) -
Pong Winnie W.,
Higer Samantha B.,
Gianino Scott M.,
Emnett Ryan J.,
Gutmann David H.
Publication year - 2013
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.23813
Subject(s) - cx3cr1 , glioma , microglia , stromal cell , neurofibromatosis , cancer research , neurofibromin 1 , chemokine , biology , carcinogenesis , pathology , neuroscience , medicine , chemokine receptor , immunology , inflammation , cancer , genetics
Although traditional models of carcinogenesis have largely focused on neoplastic cells, converging data have revealed the importance of non‐neoplastic stromal cells in influencing tumor growth and progression. Leveraging a genetically engineered mouse model of neurofibromatosis type 1 (NF1)‐associated optic glioma, we now demonstrate that stromal microglia express the CX3CR1 chemokine receptor, such that reduced CX3CR1 expression decreases optic nerve microglia. Moreover, genetic reduction of Cx3cr1 expression in Nf1 optic glioma mice delays optic glioma formation. Coupled with previous findings demonstrating that microglia maintain optic glioma growth, these new findings provide a strong preclinical rationale for the development of future stroma‐directed glioma therapies in children. ANN NEUROL 2013;73:303–308