TGF-¦Â1 enhances tumor-induced angiogenesis via JNK pathway and macrophage infiltration in an improved zebrafish embryo/xenograft glioma model

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• 作者：Xiao-jun Yang ; Gui-lai Chen ; Shi-cang Yu ; Chuan Xu ; Yan-hong Xin ; Ting-ting Li ; Yu Shi ; Ai Gu ; Jiang-jie Duan ; Chen Qian ; You-hong Cui ; Xia Zhang ; ^{zhangxia45@gmail.com} ; Xiu-wu Bian ; ^{bianxiuwu@263.net}
• 关键词：Angiogenesis ; Glioma ; JNK ; Macrophage ; TGF-¦Â1 ; Zebrafish
• 刊名：International Immunopharmacology
• 出版年：2013
• 出版时间：February, 2013
• 年：2013
• 卷：15
• 期：2
• 页码：191-198
• 全文大小：1219 K

文摘

Angiogenesis plays a crucial role at the early stage of tumorigenesis and tumor progression. A suitable model will be useful not only for the clarification of the underlying molecular mechanisms, but also for high-throughput identification of novel anti-angiogenesis compounds. Here, we established a zebrafish model for the purpose to investigate angiogenesis and screen anti-angiogenic compounds. Glioma U87 cells expressing red fluorescent protein (RFP) were transplanted in fli:GFP transgenic zebrafish embryos where significant angiogenesis was observed. TGF-¦Â1 enhanced glioma-induced angiogenesis, which was inhibited by JNK inhibitor SP600125 but not p38 MAPK inhibitor SB202190, ERK inhibitor PD98059, or PI3K inhibitor LY294002, indicating the important role of TGF-¦Â1 and JNK pathways in this process. Moreover, the glioma-induced angiogenesis was associated with macrophage infiltration that was further enhanced by TGF-¦Â1. Therefore, our zebrafish model provides a powerful in vivo tool for the investigation of tumor-induced angiogenesis, and a cost-effective system for high-throughput screening of anti-angiogenic compounds.