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

被引:721
作者
Sun, LX
Hui, AM
Su, Q
Vortmeyer, A
Kotliarov, Y
Pastorino, S
Passaniti, A
Menon, J
Walling, J
Bailey, R
Rosenblum, M
Mikkelsen, T
Fine, HA [1 ]
机构
[1] NCI, Neurooncol Branch, NINDS, NIH, Bethesda, MD 20892 USA
[2] NINDS, Dept Neurosurg, NIH, Bethesda, MD 20892 USA
[3] Univ Maryland, Sch Med, Greenebaum Canc Ctr, Baltimore, MD 21201 USA
[4] NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20814 USA
[5] Henry Ford Hosp, Hermelin Brain Tumor Ctr, Dept Neurol, Detroit, MI 48202 USA
[6] Henry Ford Hosp, Hermelin Brain Tumor Ctr, Dept Neurosurg, Detroit, MI 48202 USA
关键词
D O I
10.1016/j.ccr.2006.03.003
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:287 / 300
页数:14
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