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Title: Enhanced angiogenesis, hypoxia and neutrophil recruitment during Myc-induced liver tumorigenesis in zebrafish
Authors: Zhao Y. 
Huang X. 
Ding T.W.
Gong Z. 
Keywords: Myc protein
Myc protein, mouse
cell hypoxia
cell transformation
disease model
gene expression regulation
liver tumor
neovascularization (pathology)
neutrophil chemotaxis
organ size
tumor microenvironment
zebra fish
Cell Hypoxia
Cell Transformation, Neoplastic
Disease Models, Animal
Gene Expression Regulation, Neoplastic
Liver Neoplasms
Neovascularization, Pathologic
Neutrophil Infiltration
Organ Size
Proto-Oncogene Proteins c-myc
Tumor Microenvironment
Issue Date: 2016
Publisher: Nature Publishing Group
Citation: Zhao Y., Huang X., Ding T.W., Gong Z. (2016). Enhanced angiogenesis, hypoxia and neutrophil recruitment during Myc-induced liver tumorigenesis in zebrafish. Scientific Reports 6 : 31952. ScholarBank@NUS Repository.
Abstract: Angiogenesis, hypoxia and immune cells are important components in tumor microenvironment affecting tumor growth. Here we employed a zebrafish liver tumor model to investigate the effect of Myc expression on angiogenesis, hypoxia and tumor-infiltrated neutrophils during the tumor initiation stage. We found that induced Myc expression in the liver caused a dramatic increase of liver size with neoplastic features. The tumorigenic liver was accompanied by enhanced angiogenesis and inhibition of angiogenesis by an inhibitor (SU5416 or sunitinib) hindered the tumorigenic growth, suggesting an essential role of angiogenesis in tumorigenic growth of liver tumor in this zebrafish model. Myc induction also caused hypoxia, which could be further enhanced by hypoxia activator, ML228, to lead to a further enlargement of tumorigenic liver. Furthermore, Myc overexpression incurred an increase of liver-infiltrated neutrophils and the increase could be suppressed by angiogenesis inhibitors or by morpholino knockdown inhibition of neutrophil differentiation, leading to a suppression of growth of tumorigenic livers. Finally, the enhanced angiogenesis, hypoxia and tumor-infiltrated neutrophils by Myc overexpression were validated by RT-qPCR examination of expression of relevant biomarker genes. In sum, the current study demonstrated that the Myc-induced liver tumor model in zebrafish provides an excellent platform for study of tumor microenvironment. © The Author(s) 2016.
Source Title: Scientific Reports
ISSN: 20452322
DOI: 10.1038/srep31952
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