Dataset Information

The Role of Tumor-Associated Neutrophils in Colorectal Cancer.

ABSTRACT: Colorectal cancer (CRC) is one of the most common causes of cancer deaths worldwide and the number of CRC patients is increasing progressively. Despite the improvement of the surgical techniques and chemotherapy, we have not completely overcome this disease yet due to the metastases. Therefore, understanding the mechanisms through which metastasis occurs is important for overcoming CRC. Normal host cells in the tumor microenvironment, such as macrophages and fibroblasts, have been reported to promote the growth of CRCs. Although neutrophils were originally considered to have defensive functions against tumor cells, it has been revealed that some populations of neutrophils, called as tumor-associated neutrophils (TANs), have tumor-supportive functions. The plasticity between tumor-suppressive and -supportive neutrophils are regulated by transforming growth factor (TGF)-? and Interferon-? signaling. Some studies have demonstrated that TANs promote the spread of cancer cells to distant organs. TANs contribute to the tumor invasion and angiogenesis through the production of matrix metalloproteinase-9 (MMP9), vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF) in the primary and metastatic sites. Neutrophils also promotes tumor cell dissemination by capturing circulating tumor cells using neutrophil extracellular traps and promote their migration to distant sites. The neutrophil-to-lymphocyte ratio is a well-defined predictive marker for CRC patients. In this review, we highlight the molecular signaling between TANs and CRC cells and the possibility of TANs as a potential target for cancer therapy.

SUBMITTER: Mizuno R

PROVIDER: S-EPMC6386937 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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The Role of Tumor-Associated Neutrophils in Colorectal Cancer.

Mizuno Rei R Kawada Kenji K Itatani Yoshiro Y Ogawa Ryotaro R Kiyasu Yoshiyuki Y Sakai Yoshiharu Y

International journal of molecular sciences 20190127 3

Colorectal cancer (CRC) is one of the most common causes of cancer deaths worldwide and the number of CRC patients is increasing progressively. Despite the improvement of the surgical techniques and chemotherapy, we have not completely overcome this disease yet due to the metastases. Therefore, understanding the mechanisms through which metastasis occurs is important for overcoming CRC. Normal host cells in the tumor microenvironment, such as macrophages and fibroblasts, have been reported to pr ...[more]

PMID: 30691207

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Project description:BackgroundUlcerative colitis (UC) is a chronic inflammatory disease of the intestinal mucosa, the incidence of which has increased worldwide. There is still a lack of clear understanding of the pathogenesis of ulcerative colitis that ultimately leads to colitis-associated colorectal cancer.MethodWe download UC transcriptome data from the GEO database and pass the limma package in order to identify differentially expressed genes. Gene Set Enrichment Analysis (GSEA) was used to identify potential biological pathways. We identified immune cells associated with UC by CIBERSORT and Weighted co-expression network analysis (WGCNA). We used validation cohorts and mouse models to verify the expression of the hub genes and the role of neutrophils.ResultWe identified 65 differentially expressed genes in UC samples and healthy controls. GSEA, KEGG, and GO analyses displayed that DEGs were enriched in immune-related pathways. CIBERSORT analysis revealed increased infiltration of neutrophils in UC tissues. The red module, obtained by WGCNA analysis, was considered to be the most relevant module for neutrophils.Based on neutrophil-associated differentially expressed genes, UC patients were classified into two subtypes of neutrophil infiltration. We discovered that the highly neutrophil-infiltrated subtype B of UC patients had a higher risk of developing CAC. Five genes were identified as biomarkers by searching for DEGs between distinct subtypes. Finally, using the mouse model, we determined the expression of these five genes in the control, DSS, and AOM/DSS groups. The degree of neutrophil infiltration in mice and the percentage of MPO and pSTAT3 expression in neutrophils were analyzed by flow cytometry. In the AOM/DSS model, MPO and pSTAT3 expressions were significantly increased.ConclusionsThese findings suggested neutrophils might promote the conversion of UC into CAC. These findings improve our understanding of the pathogenesis of CAC and provide new and more effective insights into the prevention and treatment of CAC.

Dataset Information

The Role of Tumor-Associated Neutrophils in Colorectal Cancer.

Publications

The Role of Tumor-Associated Neutrophils in Colorectal Cancer.

Similar Datasets

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