Abstract
Abstract Brain tumors (gliomas) are composed of heterogeneous populations of neoplastic and non-neoplastic cells. While the neoplastic cells have classically been the target of therapeutic drug design, recent studies have demonstrated a critical role for non-neoplastic cells in brain tumor growth. The importance of non-neoplastic (stromal) cells is underscored by genetically-engineered mouse (GEM) models of Neurofibromatosis type 1 (NF1)-associated optic glioma. Whereas mice lacking Nf1 gene expression in GFAP+ glial cells do not develop brain tumors, nearly 100% of Nf1+/− mice with GFAP+ cell Nf1 inactivation form optic gliomas. These observations establish an obligate role for Nf1+/− non-neoplastic cells in gliomagenesis. One of the non-neoplastic cell types found in both mouse and human NF1-associated gliomas is microglia, a resident population of macrophage-like cells. To prove that microglia are essential drivers of glioma formation, we generated Nf1 optic glioma mice with reduced expression of the microglial chemokine receptor CX3CR1 (Nf1+/−GFAPCKO-cx3cr1+/GFP mice). Consistent with the critical role of CX3CR1 in microglial function, Nf1+/−GFAPCKO-cx3cr1+/GFP mice had reduced numbers of Iba1+ microglia in the optic nerve. Moreover, Nf1+/−GFAPCKO-cx3cr1+/GFP mice had optic glioma proliferative indices and optic nerve volumes comparable to those found in wild-type mice, demonstrating that microglia are necessary for optic nerve gliomagenesis. Collectively, these findings establish an obligate role for microglia in glioma formation and suggest that CX3CR1 is a potential target for future therapeutic drug design. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1530. doi:1538-7445.AM2012-1530
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
