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MAdCAM-1 targeting strategy can prevent colitic cancer carcinogenesis and progression via suppression of immune cell infiltration and inflammatory signals

ABSTRACT: MAdCAM-1 targeting strategy can prevent colitic cancer carcinogenesis and progression via suppression of immune cell infiltration and inflammatory signals

PROVIDER: PRJNA991527 | ENA |

REPOSITORIES: ENA

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MAdCAM-1 targeting strategy can prevent colitic cancer carcinogenesis and progression via suppression of immune cell infiltration and inflammatory signals

Project description:Chronic inflammation caused by infiltrating immune cells can promote colitis-associated dysplasia/colitic cancer in ulcerative colitis (UC) by activating inflammatory cytokine signaling through the IL-6/p-STAT3 and TNFα/NF-κB pathways. Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) expressed on high endothelial venules promotes the migration of immune cells from the bloodstream to the gut via interaction with α4β7 integrin expressed on the immune cells. MAdCAM-1, has therefore drawn interest as a novel therapeutic target for treating active UC. However, the role of MAdCAM-1-positive endothelial cells in immune cell infiltration in dysplasia/colitic cancers remains unclear. We evaluated the expression of MAdCAM-1, CD31, and immune cell markers (CD8, CD68, CD163, and FOXP3) in samples surgically resected from 11 UC patients with dysplasia/colitic cancer and 17 patients with sporadic colorectal cancer (SCRC), using immunohistochemical staining. We used an azoxymethane/dextran sodium sulfate mouse model (AOM/DSS mouse) to evaluate whether dysplasia/colitic cancer could be suppressed with an anti-MAdCAM-1 blocking antibody by preventing immune cell infiltration. The number of MAdCAM-1-positive vessels and infiltrating CD8+, CD68+, and CD163+ immune cells was significantly higher in dysplasia/colitic cancer than in normal, SCRC, and UC mucosa. In AOM/DSS mice, the anti-MAdCAM-1 antibody reduced the number, mean diameter, depth of tumors, Ki67 positivity, number of CD8+, CD68+, and CD163+ immune cells, and the IL-6/p-STAT3 and TNF-α/NF-κB signaling. Our results indicate that targeting MAdCAM-1 is a promising strategy for controlling not only UC severity, but also carcinogenesis and tumor progression by regulating inflammation/immune cell infiltration in patients with UC.

2023-07-10 | GSE236524 | GEO

Gut microbiota analysis of colitic SD rats

Project description:Fecal samples collected on day 5 from randomly selected colitic SD rats were analyzed for gut microbiota by sequencing the V4 region of the 16S rRNA gene. The orally administered Dex-P-laden NPA2 coacervate (Dex-P/NPA2) significantly restores the diversity of gut microbiota compared with colitic SD rats in the Dex-P/PBS group and the untreated colitic rats (Control).

2021-11-06 | GSE167138 | GEO

Ursolic acid regulates inflammatory cell infiltration to prevent ulcerative colitis

Project description:Ursolic acid regulates inflammatory cell infiltration to prevent ulcerative colitis

| PRJNA633156 | ENA

Gut microbiota analysis of colitic SD rats

Project description:Gut microbiota analysis of colitic SD rats

| PRJNA703055 | ENA

Excretory-secretory proteome of nematode Heligmosomoides polygyrus developed in colitic conditions

Project description:The aim of the study was to evaluate excretory-secretory protein set produced by nematode H. polygyrus L4 stage male and female developed in colitic milienu. Mass spectrometry was used to identify proteins. OmicsBox was used to investigate the functions of the discovered proteins.

2023-10-24 | PXD041516 | Pride

Metaproteomics of colonic microbiota unveils discrete protein functions among colitic mice and control groups

Project description:We utilized the well-characterized murine T cell transfer model of colitis to find specific alterations in the intestinal luminal proteome associated with inflammation. Mass spectrometry proteomic analysis of colonic samples permitted the identification of ~10,000-12,000 unique peptides that corresponded to 5610 protein clusters identified across three groups, including the colitic Rag1 -/- T cell recipients, isogenic Rag1 -/- controls, as well as wild-type mice. Bioinformatic analyses on host and microbial proteins found specific proteins and GO term functionalities unique to each group, as well as GO terms shared across the three cohorts. We further demonstrated that the colitic mice exhibited a significant increase in Proteobacteria and Verrucomicrobia that was substantiated with 16S rDNA sequencing.

2018-07-05 | PXD006384 | Pride

E-cadherin bridges cell polarity and spindle orientation to ensure prostate epithelial integrity and prevent carcinogenesis in vivo

Project description:Cell polarity and correct mitotic spindle positioning are essential for the maintenance of a proper prostate epithelial architecture, and disruption of the two biological features occurs at early stages in prostate tumorigenesis. However, whether and how these two epithelial attributes are connected in vivo is largely unknown. We herein report that conditional genetic deletion of E-cadherin, a key component of adherens junctions, in a mouse model results in loss of prostate luminal cell polarity and randomization of spindle orientations. Critically, E-cadherin ablation causes prostatic hyperplasia which progresses to invasive adenocarcinoma. Mechanistically, E-cadherin and the spindle positioning determinant LGN interacts with the PDZ domain of cell polarity protein SCRIB and form a ternary protein complex to bridge cell polarity and cell division orientation. These findings provide a novel mechanism by which E-cadherin acts an anchor to maintain prostate epithelial integrity and to prevent carcinogenesis in vivo.

2018-08-01 | GSE115204 | GEO

Immune Infiltration in Aggressive Papillary Craniopharyngioma: High infiltration But Low Action

Project description:Immune Infiltration in Aggressive Papillary Craniopharyngioma: High infiltration But Low Action

| PRJNA892989 | ENA

Expression data from epithelial cells during the process of multistep pancreatic carcinogenesis

Project description:The host antitumor immunity changes drastically during carcinogenesis. Intraductal papillary-mucinous neoplasm (IPMN) of the pancreas is a precursor lesion of pancreatic cancer and progresses according to adenoma-carcinoma sequence. We found that the host antitumor immune reaction changes from an immune response to immune tolerance between intraductal papillary-mucinous adenoma (IPMA) and intraductal papillary-mucinous carcinoma (IPMC). In order to determine molecules affecting intraepithelial DC infiltration in IPMNs during multistep carcinogenesis, we examined the gene-expression profiles of entire transcripts of neoplastic cells at different stages. We collected normal and neoplastic epithelial cells from frozen tissue sections (normal main pancreatic duct, IPMA, IPMC, and invasive carcinoma originating in IPMN) by laser microdissection, extracted total RNA from them, and analyzed their gene expression profiles using Affymetrix microarrays.

2010-12-23 | E-GEOD-19650 | biostudies-arrayexpress

E-cadherin bridges cell polarity and spindle orientation to ensure prostate epithelial integrity and prevent carcinogenesis in vivo

Project description:E-cadherin bridges cell polarity and spindle orientation to ensure prostate epithelial integrity and prevent carcinogenesis in vivo

| PRJNA474104 | ENA

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