PUBLICATION

Transcriptomic profiles of tumor-associated neutrophils reveal prominent roles in enhancing angiogenesis in liver tumorigenesis in zebrafish

Authors
Huo, X., Li, H., Li, Z., Yan, C., Agrawal, I., Mathavan, S., Liu, J., Gong, Z.
ID
ZDB-PUB-190209-3
Date
2019
Source
Scientific Reports   9: 1509 (Journal)
Registered Authors
Gong, Zhiyuan, Li, Zhen, Mathavan, S.
Keywords
none
MeSH Terms
  • Zebrafish
  • Carcinogenesis/genetics*
  • Carcinogenesis/pathology
  • Neovascularization, Pathologic/genetics*
  • Gene Expression Regulation, Neoplastic*
  • Neutrophils/metabolism
  • Neutrophils/pathology*
  • Animals
  • Humans
  • Liver Neoplasms, Experimental/blood supply*
  • Liver Neoplasms, Experimental/genetics*
  • Liver Neoplasms, Experimental/pathology
  • Gene Expression Profiling
  • Transcriptome*
  • Signal Transduction
  • Mice
(all 16)
PubMed
30728369 Full text @ Sci. Rep.
Abstract
We have previously demonstrated the pro-tumoral role of neutrophils using a kras-induced zebrafish hepatocarcinogenesis model. To further illustrate the molecular basis of the pro-tumoral role, Tumor-associated neutrophils (TANs) were isolated by fluorescence-activated cell sorting (FACS) and transcriptomic analyses were carried out by RNA-Seq. Differentially expressed gene profiles of TANs from larvae, male and female livers indicate great variations during liver tumorigenesis, but the common responsive canonical pathways included an immune pathway (Acute Phase Response Signaling), a liver metabolism-related pathway (LXR/RXR Activation) and Thrombin Signaling. Consistent with the pro-tumoral role of TANs, gene module analysis identified a consistent down-regulation of Cytotoxicity module, which may allow continued proliferation of malignant cells. Gene Set Enrichment Analysis indicated up-regulation of several genes promoting angiogenesis. Consistent with this, we found decreased density of blood vessels accompanied with decreased oncogenic liver sizes in neutrophil-depleted larvae. Collectively, our study has indicated some molecular mechanisms of the pro-tumoral roles of TANs in hepatocarcinogenesis, including weakened immune clearance against tumor cells and enhanced function in angiogenesis.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
gz15TgTransgenic Insertion
    gz37TgTransgenic Insertion
      nz50TgTransgenic Insertion
        y1TgTransgenic Insertion
          zf497TgTransgenic Insertion
            1 - 5 of 5
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            Human Disease / Model
            Human Disease Fish Conditions Evidence
            hepatocellular carcinomagz37Tgchemical treatment: doxycyclineTAS
            1 - 1 of 1
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            Sequence Targeting Reagents
            Target Reagent Reagent Type
            csf3rMO3-csf3rMRPHLNO
            1 - 1 of 1
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            Fish
            Antibodies
            No data available
            Orthology
            No data available
            Engineered Foreign Genes
            Marker Marker Type Name
            DsRedEFGDsRed
            DsRed2EFGDsRed2
            EGFPEFGEGFP
            RFPEFGRFP
            1 - 4 of 4
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            Mapping
            No data available