Sun Lixin, Hui Ai-Min, Su Qin, Vortmeyer Alexander, Kotliarov Yuri, Pastorino Sandra, Passaniti Antonino, Menon Jayant, Walling Jennifer, Bailey Rolando, Rosenblum Marc, Mikkelsen Tom, Fine Howard A
Neuro-Oncology Branch, National Cancer Institute/National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
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.
干细胞因子（SCF）在脑损伤后的神经元以及胶质瘤细胞中均有过表达；然而，其在胶质瘤发生中的作用仍不清楚。在此，我们证明SCF在体外直接激活脑微血管内皮细胞（ECs），并在体内诱导强烈的血管生成反应。原发性人类胶质瘤以分级依赖的方式表达SCF，并诱导正常神经元在被胶质瘤细胞浸润的脑区表达SCF，这些区域与显著的血管生成共定位。SCF的下调抑制体内肿瘤介导的血管生成和胶质瘤生长，而SCF的过表达与恶性胶质瘤患者的较短生存期相关。因此，SCF/c-Kit通路在脑内肿瘤和正常宿主细胞诱导的血管生成中起重要作用。
