title: TGF-β1 enhances tumor-induced angiogenesis via JNK pathway and macrophage infiltration in an improved zebrafish embryo/xenograft glioma model.
abstract: 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-β1 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-β1 and JNK pathways in this process. Moreover, the glioma-induced angiogenesis was associated with macrophage infiltration that was further enhanced by TGF-β1. 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.
authors.affiliation: Key Laboratory of Tumor Immunopathology, Third Military Medical University, Ministry of Education of China, China.
authors.forename: Xiao-jun
authors.initials: XJ
authors.lastname: Yang
authors.forename: Gui-lai
authors.initials: GL
authors.lastname: Chen
authors.forename: Shi-cang
authors.initials: SC
authors.lastname: Yu
authors.forename: Chuan
authors.initials: C
authors.lastname: Xu
authors.forename: Yan-hong
authors.initials: YH
authors.lastname: Xin
authors.forename: Ting-ting
authors.initials: TT
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Shi
authors.forename: Ai
authors.initials: A
authors.lastname: Gu
authors.forename: Jiang-jie
authors.initials: JJ
authors.lastname: Duan
authors.forename: Chen
authors.initials: C
authors.lastname: Qian
authors.forename: You-hong
authors.initials: YH
authors.lastname: Cui
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
authors.forename: Xiu-wu
authors.initials: XW
authors.lastname: Bian
mesh_terms: D020533:Angiogenesis Inhibitors / Q000302:isolation & purification*; D000818:Animals; D030801:Animals, Genetically Modified; D000873:Anthracenes / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D005419:Flavonoids / Q000494:pharmacology; D005910:Glioma / Q000098:blood supply*; D057166:High-Throughput Screening Assays; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors; D008264:Macrophages / Q000187:drug effects; D009025:Morpholines / Q000494:pharmacology; D009389:Neovascularization, Pathologic; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays; D015027:Zebrafish
chemical_list: D020533:Angiogenesis Inhibitors; D000873:Anthracenes; D002867:Chromones; D005419:Flavonoids; D007093:Imidazoles; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011725:Pyridines; D053773:Transforming Growth Factor beta1; C432165:pyrazolanthrone; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D048049:Extracellular Signal-Regulated MAP Kinases; D048670:MAP Kinase Kinase 4; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one