Reduced microglial CX3CR1 expression delays neurofibromatosis-1 glioma formation

Ann Neurol. 2013 Feb;73(2):303-8. doi: 10.1002/ana.23813. Epub 2013 Feb 19.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Stem / pathology
  • Brain Stem / physiology
  • CX3C Chemokine Receptor 1
  • Disease Models, Animal
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microglia / pathology
  • Microglia / physiology*
  • Neurofibromatosis 1 / genetics
  • Neurofibromatosis 1 / pathology*
  • Neurofibromin 1 / genetics
  • Optic Nerve / pathology
  • Optic Nerve / physiology*
  • Optic Nerve Glioma / genetics
  • Optic Nerve Glioma / pathology*
  • Receptors, Chemokine / genetics*

Substances

  • CX3C Chemokine Receptor 1
  • Cx3cr1 protein, mouse
  • Neurofibromin 1
  • Receptors, Chemokine