Fusobacterium nucleatum promotes M2 polarization of macrophages in the microenvironment of colorectal tumours via a TLR4-dependent mechanism

AbstractFusobacterium nucleatum (Fn) has been shown to promote colorectal cancer (CRC) development by inhibiting host anti-tumour immunity. However, the impact ofFn infection on macrophage polarization and subsequent intestinal tumour formation as well as the underlying molecular pathways has not been investigated. We investigated the impact ofFn infection on macrophage polarization in human CRCs and cultured macrophages as well as the effects on macrophage phenotype and intestinal tumour formation inApcMin/+ mice. We also examined whether macrophage-polarized activation challenged byFn infection via a TLR4-dependent mechanism involved the IL-6/STAT3/c-MYC signalling cascade. Our data showed that macrophages are a major tumour-infiltrating immune cell type in human CRCs withFn infection (P 
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research

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Authors: Hernández-Luna MA, López-Briones S, Luria-Pérez R Abstract Worldwide, neoplasms of the gastrointestinal tract have a very high incidence and mortality. Among these, colorectal cancer, which includes colon and rectum malignancies, representing both highest incidence and mortality. While gallbladder cancer, another neoplasm associated to gastrointestinal tract occurs less frequently. Genetic factors, inflammation and nutrition are important risk factors associated with colorectal cancer development. Likewise, pathogenic microorganisms inducing intestinal dysbiosis have become an importan...
Source: Journal of Oncology - Category: Cancer & Oncology Tags: J Oncol Source Type: research
Baojun Xu Colorectal patients generally have the maximum counts of Fusobacterium nucleatum (F. nucleatum) in tumors and elevate colorectal adenomas and carcinomas, which show the lowest rate of human survival. Hence, F. nucleatum is a diagnostic marker of colorectal cancer (CRC). Studies demonstrated that targeting fusobacterial Fap2 or polysaccharide of the host epithelium may decrease fusobacteria count in the CRC. Attenuated F. nucleatum-Fap2 prevents transmembrane signals and inhibits tumorigenesis inducing mechanisms. Hence, in this review, we hypothesized that application of genetically programmed fusobacterium c...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
ConclusionAlteration in the cell cycle by means of different mechanisms such as inflammation, alteration in cell signaling, invasion and immune evasion, specific niche colonization, induction of DNA damage and mutation, expression of some microRNAs, and enhancing epigenetic effects are the most common mechanisms employed by bacterial species.
Source: Journal of Gastrointestinal Cancer - Category: Cancer & Oncology Source Type: research
This study evaluatedF. nucleatum as a prognostic biomarker, by assessing its association with post-diagnosis survival from CRC. From September 2008 to April 2012 CRC patients (n = 190) were recruited from three hospitals within the Czech Republic.F. nucleatum DNA copies were measured in adjacent non-malignant and colorectal tumor tissues using quantitative real-time PCR. Cox Proportional Hazards (HR) models were applied to evaluate the association betweenF. nucleatum DNA and overall survival, adjusting for key confounders. Risk prediction modeling was conducted to evaluate the ability to predict survival based onF. nucleat...
Source: European Journal of Clinical Microbiology and Infectious Diseases - Category: Microbiology Source Type: research
In this study, the effects of COS on colorectal cancer (CRC) development were evaluated using azoxymethane and dextran sulfate sodium (AOM/DSS) induced mouse model of CRC (CACM). In the COS-treated CRC group (CMCOS), COS protected mice from CRC by decreasing the disease activity index, tumor incidences and multiplicity, and the mRNA levels of COX-2, IL-6, TNF-α, IL-1β, IL-10, and IKK-β mRNA in colonic epithelial cells. The results of a cage-exchanged experiment, in which mice from the CACMe and CMCOSe treatments exchanged cages every day to interact with microbes, showed that gut microbes play an important ...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
AbstractPurpose of ReviewTo summarize the relationship between colorectal cancer (CRC), immunity, and the gut microbiome, focusing on the population ofFusobacterium, particularlyFusobacterium nucleatum, which may mediate CRC initiation and progression by inhibiting host anti-tumor immunity.Recent FindingsThe onset and advancement of CRC involves genetic and epigenetic alterations and are modified by dietary and environmental factors. There is increasing evidence suggesting that gut bacteria, such asFusobacterium nucleatum, may promote CRC development. The mechanisms through whichFusobacterium nucleatum from the oral cavity...
Source: Current Colorectal Cancer Reports - Category: Cancer & Oncology Source Type: research
To investigate the clinicopathological features and prognostic impact of Fusobacterium nucleatum (F nucleatum) status in patients with colorectal cancer (CRC) and its relationships with microsatellite instability (MSI) status. Retrospective analysis of consecutive 91 CRC tissues from surgically resected specimens of stage III or high-risk stage II CRC patients who had received curative surgery in Wuhan Union Hospital from January, 2017 to January, 2019 was conducted. F nucleatum DNA was quantitatively measured and classified into 1 of the 2 categories: F nucleatum-high, or F nucleatum-low/negative. The Cox risk ratio mode...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Observational Study Source Type: research
Microbial diversity has been pointed as a major factor in the development and progression of colorectal cancer (CRC). We sought to explore the richness and abundance of the microbial community of a series of colorectal tumor samples treated at Barretos Cancer Hospital, Brazil, through 16S rRNA sequencing. The presence and the impact of Fusobacterium nucleatum (Fn) DNA in CRC prognosis was further evaluated by qPCR in a series of 152 colorectal cancer cases. An enrichment for potentially oncogenic bacteria in CRC was observed, with Fusobacterium being the most abundant genus in the tumor tissue. In the validation dataset, F...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Abstract Gut microbiota and their metabolites play a vital role in colon health and disease. Accumulating evidence suggests that the gut microbiota contributes to the risk of colorectal cancer (CRC). However, the role of a specific microbial community together with their metabolites contributing to the risk, initiation and progression of CRC is still unknown. Hence, we used a Bayesian Networks in combination with the IDA (Intervention calculus when the DAG is absent) to generate a graphical model that allows causal relationships to be inferred from observational data. Results from the analysis of publically availa...
Source: Bioinformation - Category: Bioinformatics Authors: Tags: Bioinformation Source Type: research
Colorectal cancer (CRC) is the third most prevalent cancer and second in terms of mortality (1). Emerging evidence from recent studies suggests a potential role of Fusobacterium nucleatum in the development of CRC. In this article, we review studies from different geographical regions examining the association between F. nucleatum and CRC, the detection methods and the tumorigenic mechanisms. Furthermore, we discuss the potential clinical impact of F. nucleatum in CRC and suggest future study directions.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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