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.

journal_name

Int Immunopharmacol

authors

Yang XJ,Chen GL,Yu SC,Xu C,Xin YH,Li TT,Shi Y,Gu A,Duan JJ,Qian C,Cui YH,Zhang X,Bian XW

doi

10.1016/j.intimp.2012.12.002

subject

Has Abstract

pub_date

2013-02-01 00:00:00

pages

191-8

issue

2

eissn

1567-5769

issn

1878-1705

pii

S1567-5769(12)00364-5

journal_volume

15

pub_type

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