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
  • Animals
  • Carcinogenesis/genetics*
  • Carcinogenesis/pathology
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Liver Neoplasms, Experimental/blood supply*
  • Liver Neoplasms, Experimental/genetics*
  • Liver Neoplasms, Experimental/pathology
  • Mice
  • Neovascularization, Pathologic/genetics*
  • Neutrophils/metabolism
  • Neutrophils/pathology*
  • Signal Transduction
  • Transcriptome*
  • Zebrafish
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
Figure Gallery
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Errata and Notes