Dataset Information

SARI suppresses colitis-associated cancer development by maintaining MCP-1-mediated tumour-associated macrophage recruitment.

ABSTRACT: SARI (suppressor of AP-1, regulated by IFN) impaired tumour growth by promoting apoptosis and inhibiting cell proliferation and tumour angiogenesis in various cancers. However, the role of SARI in regulating tumour-associated inflammation microenvironment is still elusive. In our study, the colitis-dependent and -independent primary model were established in SARI deficiency mice and immuno-reconstructive mice to investigate the functional role of SARI in regulating tumour-associated inflammation microenvironment and primary colon cancer formation. The results have shown that SARI deficiency promotes colitis-associated cancer (CAC) development only in the presence of colon inflammation. SARI inhibited tumour-associated macrophages (TAM) infiltration in colon tissues, and SARI deficiency in bone marrow cells has no observed role in the promotion of intestinal tumorigenesis. Mechanism investigations indicated that SARI down-regulates p-STAT1 and STAT1 expression in colon cancer cells, following inhibition of MCP-1/CCR2 axis activation during CAC development. Inverse correlations between SARI expression and macrophage infiltration, MCP-1 expression and p-STAT1 expression were also demonstrated in colon malignant tissues. Collectively, our results prove the inhibition role of SARI in colon cancer formation through regulating TAM infiltration.

SUBMITTER: Dai L

PROVIDER: S-EPMC6933368 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

SARI suppresses colitis-associated cancer development by maintaining MCP-1-mediated tumour-associated macrophage recruitment.

Dai Lei L Liu Yi Y Yin Yuan Y Li Junshu J Dong Zhexu Z Chen Na N Cheng Lin L Wang Huiling H Fang Chao C Lin Yi Y Shi Gang G Zhang Hantao H Fan Ping P Su Xiaolan X Zhang Shuang S Yang Yang Y Yang Lie L Huang Wei W Zhou Zongguang Z Yu Dechao D Deng Hongxin H

Journal of cellular and molecular medicine 20191002 1

SARI (suppressor of AP-1, regulated by IFN) impaired tumour growth by promoting apoptosis and inhibiting cell proliferation and tumour angiogenesis in various cancers. However, the role of SARI in regulating tumour-associated inflammation microenvironment is still elusive. In our study, the colitis-dependent and -independent primary model were established in SARI deficiency mice and immuno-reconstructive mice to investigate the functional role of SARI in regulating tumour-associated inflammation ...[more]

PMID: 31578820

Similar Datasets

Project description:Epidermal growth factor receptor (EGFR) signaling is a known mediator of colorectal carcinogenesis. Studies have focused on the role of EGFR signaling in epithelial cells, although the exact nature of the role of EGFR in colorectal carcinogenesis remains a topic of debate. Here, we present evidence that EGFR signaling in myeloid cells, specifically macrophages, is critical for colon tumorigenesis in the azoxymethane-dextran sodium sulfate (AOM-DSS) model of colitis-associated carcinogenesis (CAC). In a human tissue microarray, colonic macrophages demonstrated robust EGFR activation in the pre-cancerous stages of colitis and dysplasia. Utilizing the AOM-DSS model, mice with a myeloid-specific deletion of Egfr had significantly decreased tumor multiplicity and burden, protection from high-grade dysplasia and significantly reduced colitis. Intriguingly, mice with gastrointestinal epithelial cell-specific Egfr deletion demonstrated no differences in tumorigenesis in the AOM-DSS model. The alterations in tumorigenesis in myeloid-specific Egfr knockout mice were accompanied by decreased macrophage, neutrophil and T-cell infiltration. Pro-tumorigenic M2 macrophage activation was diminished in myeloid-specific Egfr-deficient mice, as marked by decreased Arg1 and Il10 mRNA expression and decreased interleukin (IL)-4, IL10 and IL-13 protein levels. Surprisingly, diminished M1 macrophage activation was also detectable, as marked by significantly reduced Nos2 and Il1b mRNA levels and decreased interferon (IFN)-γ, tumor necrosis factor (TNF)-α and IL-1β protein levels. The alterations in M1 and M2 macrophage activation were confirmed in bone marrow-derived macrophages from mice with the myeloid-specific Egfr knockout. The combined effect of restrained M1 and M2 macrophage activation resulted in decreased production of pro-angiogenic factors, CXCL1 and vascular endothelial growth factor (VEGF), and reduced CD31+ blood vessels, which likely contributed to protection from tumorigenesis. These data reveal that EGFR signaling in macrophages, but not in colonic epithelial cells, has a significant role in CAC. EGFR signaling in macrophages may prove to be an effective biomarker of CAC or target for chemoprevention in patients with inflammatory bowel disease.

Dataset Information

SARI suppresses colitis-associated cancer development by maintaining MCP-1-mediated tumour-associated macrophage recruitment.

Publications

SARI suppresses colitis-associated cancer development by maintaining MCP-1-mediated tumour-associated macrophage recruitment.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets