Neuronal and glioma-derived stem cell factor induces angiogenesis within the brain

Cancer Cell. 2006 Apr;9(4):287-300. doi: 10.1016/j.ccr.2006.03.003.


Stem cell factor (SCF) is overexpressed by neurons following brain injury as well as by glioma cells; however, its role in gliomagenesis remains unclear. Here, we demonstrate that SCF directly activates brain microvascular endothelial cells (ECs) in vitro and induces a potent angiogenic response in vivo. Primary human gliomas express SCF in a grade-dependent manner and induce normal neurons to express SCF in brain regions infiltrated by glioma cells, areas that colocalize with prominent angiogenesis. Downregulation of SCF inhibits tumor-mediated angiogenesis and glioma growth in vivo, whereas overexpression of SCF is associated with shorter survival in patients with malignant gliomas. Thus, the SCF/c-Kit pathway plays an important role in tumor- and normal host cell-induced angiogenesis within the brain.

MeSH terms

  • Animals
  • Brain / blood supply*
  • Brain / drug effects
  • Brain / metabolism*
  • Cells, Cultured
  • Down-Regulation
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / metabolism
  • Fibroblast Growth Factors / pharmacology
  • Gene Expression Regulation, Neoplastic
  • Glioma / blood supply*
  • Glioma / genetics
  • Glioma / metabolism*
  • Glioma / pathology
  • Humans
  • Mice
  • Neurons / metabolism*
  • Protein Binding
  • Proto-Oncogene Proteins c-kit / metabolism
  • RNA, Small Interfering / genetics
  • Signal Transduction
  • Stem Cell Factor / genetics
  • Stem Cell Factor / metabolism*
  • Stem Cell Factor / pharmacology
  • Survival Rate


  • RNA, Small Interfering
  • Stem Cell Factor
  • fibroblast growth factor 13
  • Fibroblast Growth Factors
  • Proto-Oncogene Proteins c-kit