Dataset Information

Deletion of TNF in Winnie-APC^Min/+ Mice Reveals Its Dual Role in the Onset and Progression of Colitis-Associated Colorectal Cancer.

ABSTRACT: Colorectal cancer (CRC) is among the best examples for depicting the relationship between inflammation and cancer. The introduction of new therapeutics targeting inflammatory mediators showed a marked decrease in the overall risk of CRC, although their chemopreventive potential is still debated. Specifically, a monoclonal antibody that blocks tumor necrosis factor (TNF), infliximab, increases CRC risk in inflammatory bowel disease patients. To address the axis between TNF and CRC development and progression, we depleted the Tnf from our previously established murine model of colitis-associated cancer (CAC), the Winnie-Apc^Min/+ line. We characterized the new Winnie-APC^Min/+-TNF-KO line through macroscopical and microscopical analyses. Surprisingly, the latter demonstrated that the deletion of Tnf in Winnie-Apc^Min/+ mice resulted in an initial reduction in dysplastic lesion incidence in 5-week-old mice followed by a faster disease progression at 8 weeks. Histological data were confirmed by the molecular profiling obtained from both the real-time PCR analysis of the whole tissue and the RNA sequencing of the macrodissected tumoral lesions from Winnie-APC^Min/+-TNF-KO distal colon at 8 weeks. Our results highlight that TNF could exert a dual role in CAC, supporting the promotion of neoplastic lesions onset in the early stage of the disease while inducing their reduction during disease progression.

SUBMITTER: Verna G

PROVIDER: S-EPMC9737576 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Deletion of TNF in Winnie-<i>APC<sup>Min/+</sup></i> Mice Reveals Its Dual Role in the Onset and Progression of Colitis-Associated Colorectal Cancer.

Verna Giulio G Liso Marina M Cavalcanti Elisabetta E Armentano Raffaele R Miraglia Alessandro A Monsurrò Vladia V Chieppa Marcello M De Santis Stefania S

International journal of molecular sciences 20221202 23

Colorectal cancer (CRC) is among the best examples for depicting the relationship between inflammation and cancer. The introduction of new therapeutics targeting inflammatory mediators showed a marked decrease in the overall risk of CRC, although their chemopreventive potential is still debated. Specifically, a monoclonal antibody that blocks tumor necrosis factor (TNF), infliximab, increases CRC risk in inflammatory bowel disease patients. To address the axis between TNF and CRC development and ...[more]

PMID: 36499472

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Project description:BackgroundProgression of Colorectal cancer (CRC) is influenced by single or compounded environmental factors. Accumulating evidence shows that microbiota can influence the outcome of cancer immunotherapy. T cell, one of the main populations of effector immune cells in antitumor immunity, has been considered as a double-edged sword during the progression of CRC. Our previous studies indicate that traditional Chinese herbs (TCM) have potential anticancer effects in improving quality of life and therapeutic effect. However, little is known about the mechanism of TCM formula in cancer prevention.MethodsHere, we used C57BL/6 J ApcMin/+ mice, an animal model of human intestinal tumorigenesis, to investigate the gut bacterial diversity and their mechanisms of action in gastrointestinal adenomas, and to evaluate the effects of Yi-Yi-Fu-Zi-Bai-Jiang-San (YYFZBJS) on of colon carcinogenesis in vivo and in vitro. Through human-into-mice fecal microbiota transplantation (FMT) experiments from YYFZBJS volunteers or control donors, we were able to differentially modulate the tumor microbiome and affect tumor growth as well as tumor immune infiltration.ResultsWe report herein, YYFZBJS treatment blocked tumor initiation and progression in ApcMin/+ mice with less change of body weight and increased immune function. Moreover, diversity analysis of fecal samples demonstrated that YYFZBJS regulated animal's natural gut flora, including Bacteroides fragilis, Lachnospiraceae and so on. Intestinal tumors from conventional and germ-free mice fed with stool from YYFZBJS volunteers had been decreased. Some inflammation' expression also have been regulated by the gut microbiota mediated immune cells. Intestinal lymphatic, and mesenteric lymph nodes (MLN), accumulated CD4+ CD25+ Foxp3 positive Treg cells were reduced by YYFZBJS treatment in ApcMin/+ mice. Although YYFZBJS had no inhibition on CRC cell proliferation by itself, the altered Tregs mediated by YYFZBJS repressed CRC cancer cell growth, along with reduction of the phosphorylation of β-catenin.ConclusionsIn conclusion, we demonstrated that gut microbiota and Treg were involved in CRC development and progression, and we propose YYFZBJS as a new potential drug option for the treatment of CRC. Video abstract.

Dataset Information

Deletion of TNF in Winnie-APC^Min/+ Mice Reveals Its Dual Role in the Onset and Progression of Colitis-Associated Colorectal Cancer.

Publications

Deletion of TNF in Winnie-<i>APC<sup>Min/+</sup></i> Mice Reveals Its Dual Role in the Onset and Progression of Colitis-Associated Colorectal Cancer.

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Dataset Information

Deletion of TNF in Winnie-APCMin/+ Mice Reveals Its Dual Role in the Onset and Progression of Colitis-Associated Colorectal Cancer.

Publications

Deletion of TNF in Winnie-<i>APC<sup>Min/+</sup></i> Mice Reveals Its Dual Role in the Onset and Progression of Colitis-Associated Colorectal Cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Deletion of TNF in Winnie-APC^Min/+ Mice Reveals Its Dual Role in the Onset and Progression of Colitis-Associated Colorectal Cancer.