Dataset Information

Bifidobacterium adolescentis induces Decorin⁺ macrophages via TLR2 to suppress colorectal carcinogenesis.

ABSTRACT:

Background

The interplay between gut microbiota and tumor microenvironment (TME) in the pathogenesis of colorectal cancer (CRC) is largely unknown. Here, we elucidated the functional role of B. adolescentis and its possible mechanism on the manipulation of Decorin⁺ macrophages in colorectal cancer.

Methods

The relative abundance of B. adolescentis in tumor or para-tumor tissue of CRC patients was analyzed. The role of B. adolescentis was explored in the CRC animal models. The single cell-RNA sequencing (scRNA-seq) was used to investigate the myeloid cells subsets in TME. The expression level of TLR2/YAP axis and its downstream Decorin in macrophages were tested by Western blot and qRT-PCR. Knockdown of Decorin in Raw264.7 was performed to investigate the effect of Decorin⁺ macrophages on subcutaneous tumor formation. Multi-immunofluorescence assay examined the number of Decorin⁺ macrophages on the CRC tissue.

Results

We found that the abundance of B. adolescentis was significantly reduced in tumor tissue of CRC patients. Supplementation with B. adolescentis suppressed AOM/DSS-induced tumorigenesis in mice. ScRNA-seq and animal experiment revealed that B. adolescentis increased Decorin⁺ macrophages. Mechanically, Decorin was activated by TLR2/YAP axis in macrophages. The abundance of B. adolescentis was correlated with the number of Decorin⁺ macrophages and the expression level of TLR2 in tumor tissue of CRC patients.

Conclusions

These results highlight that B. adolescentis induced Decorin⁺ macrophages and provide a novel therapeutic target for probiotic-based modulation of immune microenvironment in CRC.

SUBMITTER: Lin Y

PROVIDER: S-EPMC10353206 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Publications

Bifidobacterium adolescentis induces Decorin<sup>+</sup> macrophages via TLR2 to suppress colorectal carcinogenesis.

Lin Yifeng Y Fan Lina L Qi Yadong Y Xu Chaochao C Jia Dingjiacheng D Jiang Yao Y Chen Shujie S Wang Liangjing L

Journal of experimental & clinical cancer research : CR 20230718 1

<h4>Background</h4>The interplay between gut microbiota and tumor microenvironment (TME) in the pathogenesis of colorectal cancer (CRC) is largely unknown. Here, we elucidated the functional role of B. adolescentis and its possible mechanism on the manipulation of Decorin<sup>+</sup> macrophages in colorectal cancer.<h4>Methods</h4>The relative abundance of B. adolescentis in tumor or para-tumor tissue of CRC patients was analyzed. The role of B. adolescentis was explored in the CRC animal model ...[more]

PMID: 37464382

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Project description:Hepatocellular carcinoma represents one of the most-rapidly spreading cancers in the world. In the majority of cases, an inflammation-driven fibrosis or cirrhosis precedes the development of the tumor. During malignant transformation, the tumor microenvironment undergoes qualitative and quantitative changes that modulate the behavior of the malignant cells. A key constituent for the hepatic microenvironment is the small leucine-rich proteoglycan decorin, known to interfere with cellular events of tumorigenesis mainly by blocking various receptor tyrosine kinases (RTK) such as EGFR, Met, IGF-IR, PDGFR and VEGFR2. In this study, we characterized cell signaling events evoked by decorin deficiency in two experimental models of hepatocarcinogenesis using thioacetamide or diethyl nitrosamine as carcinogens. Genetic ablation of decorin led to enhanced tumor occurrence as compared to wild-type animals. These findings correlated with decreased levels of the cyclin-dependent kinase inhibitor p21(WAF1/CIP1) and a concurrent elevation in retinoblastoma protein phosphorylation via cyclin dependent kinase 4. Decreased steady state p21(Waf1/Cip1) levels correlated with enhanced expression of transcription factor AP4, a known transcriptional repressor of p21(Waf1/Cip1), and enhanced c-Myc protein levels. In addition, translocation of β-catenin was a typical event in diethyl nitrosamine-evoked tumors. In parallel, decreased phosphorylation of both c-Myc and β-catenin was observed in Dcn(-/-) livers likely due to the hindered GSK3β-mediated targeting of these proteins to proteasomal degradation. We discovered that in a genetic background lacking decorin, four RTKs were constitutively activated (phosphorylated), including three known targets of decorin such as PDGFRα, EGFR, IGF-IR, and a novel RTK MSPR/RON. Our findings provide powerful genetic evidence for a crucial in vivo role of decorin during hepatocarcinogenesis as lack of decorin in the liver and hepatic stroma facilitates experimental carcinogenesis by providing an environment devoid of this potent pan-RTK inhibitor. Thus, our results support future utilization of decorin as an antitumor agent in liver cancer.

Dataset Information

Bifidobacterium adolescentis induces Decorin⁺ macrophages via TLR2 to suppress colorectal carcinogenesis.

Background

Methods

Results

Conclusions

Publications

Bifidobacterium adolescentis induces Decorin<sup>+</sup> macrophages via TLR2 to suppress colorectal carcinogenesis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Bifidobacterium adolescentis induces Decorin+ macrophages via TLR2 to suppress colorectal carcinogenesis.

Background

Methods

Results

Conclusions

Publications

Bifidobacterium adolescentis induces Decorin<sup>+</sup> macrophages via TLR2 to suppress colorectal carcinogenesis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Bifidobacterium adolescentis induces Decorin⁺ macrophages via TLR2 to suppress colorectal carcinogenesis.