[Activation of CXCR4 in human glioma stem cells promotes tumor angiogenesis].

作者：Yi‐Fang Ping, Xiaohong Yao, Xiu‐Wu Bian, Jianhong Chen, Rong Zhang, Liang Yi, Zhihua Zhou · 发表于：PubMed · 年份：2007 · 被引用次数：12 · 研究领域：Cancer Cells and Metastasis、Chemokine receptors and signaling、Immune cells in cancer

OBJECTIVE: To isolate, culture and identify glioma stem cells from human malignant glioma cell line U87, and investigate the changes of pro-angiogenic factors production by glioma stem cells followed by activation of CXCR4 and observe their tumorigenesis as well as the expression of vascular endothelial growth factor when implanted into nude mice. METHODS: The ratio of CD133 positive cells was detected by flow cytometry. Magnetic separation of CD133 positive cells was carried out on the magnetic cell sorting system (MACS). Expression of nestin, glial fibrillary acidic protein (GFAP) and CXCR4 on tumorspheres was detected by indirect immunofluorescence under confocal laser scanning microscopy. The functional activation of CXCR4 was assessed by calcium mobilization experiments. ELISA was used to detect the production of vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) in conditioned medium. Glioma stem cells were implanted into nude mice to assess their tumorigenesis ability and the expression of VEGF. RESULTS: The ratio of CD133 positive cells with stem cell property was 0.5% in U87 cells. Activation of CXCR4 on glioma stem cells induced calcium mobilization and increased VEGF and IL-8 protein secretion. CD133 positive cells secreted more VEGF and IL-8 than their negative counterparts in vitro. Tumors derived from CD133 positive cells grew more rapidly and expressed elevated level of VEGF than their negative counterparts. CONCLUSIONS: There are a small fracti...