PUBLICATION

Enhanced angiogenesis, hypoxia and neutrophil recruitment during Myc-induced liver tumorigenesis in zebrafish

Authors
Zhao, Y., Huang, X., Ding, T.W., Gong, Z.
ID
ZDB-PUB-160824-5
Date
2016
Source
Scientific Reports   6: 31952 (Journal)
Registered Authors
Gong, Zhiyuan
Keywords
Cancer genetics, Cancer microenvironment
MeSH Terms
  • Gene Expression Regulation, Neoplastic
  • Zebrafish
  • Disease Models, Animal
  • Liver Neoplasms/blood supply
  • Liver Neoplasms/genetics*
  • Liver Neoplasms/immunology*
  • Organ Size
  • Cell Hypoxia
  • Humans
  • Neutrophil Infiltration
  • Neovascularization, Pathologic/genetics*
  • Neovascularization, Pathologic/immunology
  • Tumor Microenvironment
  • Proto-Oncogene Proteins c-myc/genetics*
  • Proto-Oncogene Proteins c-myc/metabolism
  • Cell Transformation, Neoplastic/genetics*
  • Cell Transformation, Neoplastic/immunology
  • Animals
(all 18)
PubMed
27549025 Full text @ Sci. Rep.
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.
Genes / Markers
Figures
Figure Gallery (6 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
gz15Tg; gz26Tgchemical treatment by environment: doxycyclineDays 7-13
gz15Tg; gz26Tgchemical treatment by environment: doxycycline, chemical treatment by environment: semaxanibDays 7-13
gz15Tg; gz26Tgchemical treatment by environment: doxycycline, chemical treatment by environment: sunitinibDays 7-13
gz15Tg; gz26Tg; y1Tgchemical treatment by environment: doxycyclineDays 7-13
gz15Tg; gz26Tg; y1Tgchemical treatment by environment: doxycyclineDays 7-13
gz26Tgchemical treatment by environment: doxycyclineDays 30-44
gz26Tgchemical treatment by environment: doxycyclineDays 30-44
gz26Tgchemical treatment by environment: doxycyclineDays 30-44
gz26Tgchemical treatment by environment: doxycyclineDays 30-44
gz26Tgchemical treatment by environment: doxycyclineDays 30-44
1 - 10 of 23
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
gz15TgTransgenic Insertion
    gz26TgTransgenic Insertion
      rj30TgTransgenic Insertion
        sh144TgTransgenic Insertion
          y1TgTransgenic Insertion
            1 - 5 of 5
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            Human Disease / Model
            Human Disease Fish Conditions Evidence
            hepatocellular carcinomaTAS
            1 - 1 of 1
            Show
            Sequence Targeting Reagents
            Target Reagent Reagent Type
            csf3rMO3-csf3rMRPHLNO
            1 - 1 of 1
            Show
            Fish
            Fish
            gz15Tg; gz26Tg
            gz15Tg; gz26Tg; y1Tg
            gz26Tg
            gz26Tg; rj30Tg
            gz26Tg; rj30Tg + MO3-csf3r
            gz26Tg; sh144Tg
            1 - 6 of 6
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            Antibodies
            No data available
            Orthology
            No data available
            Engineered Foreign Genes
            Marker Marker Type Name
            DsRedEFGDsRed
            EGFPEFGEGFP
            GFPEFGGFP
            1 - 3 of 3
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            Mapping
            No data available
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            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.