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Genome-wide analysis of gene expression in mouse pancreas tumors [FAP and aSMA depletion]

ABSTRACT: Genome-wide analysis of gene expression in mouse pancreas tumors [FAP and aSMA depletion]

PROVIDER: PRJNA493627 | ENA |

REPOSITORIES: ENA

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Genome-wide analysis of gene expression in mouse pancreas tumors [FAP and aSMA depletion]

Project description:Gene expression analysis of pancreatic tumors from genetically engineered mice (Pdx-Cre;LSL-KRASG12D;TGFBRIIf/f) with depletion of aSMA+ or FAP+ cells. The pancreas tumors were harvested and analysed for gene expression profiles comparisons.

2018-09-28 | GSE120577 | GEO

Transcriptomic profiling of FAP+ fibroblasts

Project description:FAP+ cells had been reported to be present only in healing wounds and at sites of tissue remodelling. We have found FAP+ cells in many normal tissues and aimed to investigate whether these cells were related or whether FAP is upregulated in response to an external stimulus on a variety of cells. Furthermore we wanted to investigate whether FAP+ cells are simply fibroblasts and so compared their transcriptomic profiles to that of a typical fibroblastic population, the murine embryonic fibroblast. FAP+ cells were sorted from two mesenchymal tissues, visceral adipose and skeletal muscle, and from an epithelial organ, the pancreas. These were compared to MEFs. Cells were isolated in duplicate experiments and these were analysed separately. These were compared to previously published publically available CD4+ T-cell subset data.

2013-07-15 | E-GEOD-39438 | biostudies-arrayexpress

Genome-wide analysis of gene expression in mouse pancreas tumors

Project description:Genetically engineered mice developed spontaneous pancreas cancer (Pdx-Cre;LSL-KRASG12D;P53Mut). Mice were also engineered to develop similar spontaneous pancreas cancer without Twist or Snail (conditional gene knockout). The pancreas tumors were harvested and analysed for gene expression profiles comparisons. Total RNA was isolated from the pancreas tumors of 2 mice with wild-type Twist and Snail, from 2 mice without Twist expression in the pancreas, and from 2 mice without Snail expression in the pancreas.

2015-11-20 | E-GEOD-66981 | biostudies-arrayexpress

Genome-wide analysis of gene expression in mouse pancreas tumors

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Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 in pancreas cancer

Project description:An autochthonous model of pancreatic ductal adenocarcinoma (PDA) permitted the analysis of why immunotherapy is ineffective in this human disease. Despite finding that PDA-bearing mice had cancer cell-specific CD8+ T cells, the mice, like human PDA patients, did not respond to two immunological checkpoint antagonists that promote the function of T cells, α-CTLA-4 and α-PD-L1. Immune control of PDA growth was achieved, however, by depleting carcinoma-associated fibroblasts (CAFs) that express Fibroblast Activation Protein (FAP). The depletion of the FAP+ stromal cell also uncovered the anti-tumor effects of α-CTLA-4 and α-PD-L1, indicating that its immune suppressive activity accounts for the failure of these T cell checkpoint antagonists. Three findings suggested that CXCL12 explained the overriding immunosuppression by the FAP+ cell: T cells were absent from regions of the tumor containing cancer cells; cancer cells were coated with the chemokine, CXCL12; and the FAP+ CAF was the principle source of CXCL12 in the tumor. Administering AMD3100, a CXCL12 receptor (CXCR4) inhibitor, induced rapid T cell accumulation among cancer cells, and acted synergistically with α-PD-L1 to selectively and greatly diminish cancer cells, identified by their loss-of-heterozygosity (LOH) of Trp53. The residual tumor was comprised only of pre-malignant epithelial cells and inflammatory cells. Thus, a single protein, CXCL12, from a single stromal cell type, the FAP+ CAF, may direct tumor immune evasion in a model of human PDA.

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MicroRNA expression in sporadic and FAP-associated Desmoid Tumors and correlation with beta-catenin gene mutations

Project description:Desmoid tumors (DT) are rare, benign, fibroblastic neoplasm with challenging histological diagnosis. DTs can occur sporadically or associated with the familial adenomatous polyposis coli (FAP). Most sporadic DTs are associated with β-catenin gene (CTNNB1) mutations, while mutated APC gene causes FAP disease. MicroRNAs (miRNAs) are involved in many human carcinogenesis. The miRNA profile was analyzed by microarray in formalin-fixed, paraffin-embedded (FFEP) specimens of 12 patients (8 sporadic, 4 FAP-associated) and 4 healthy controls. One hundred and one miRNAs were dysregulated, of which 98 miRNAs in sporadic DTs, 8 in FAP-associated DTs, 5 were shared by both tumors. Twenty-six miRNAs were then validated by RT-qPCR in 23 sporadic and 7 FAP-associated DT samples matched with healthy controls. The same qPCR method was used to evaluate the CTNNB1 mutational status in sporadic DTs. The correlation between sporadic DTs and miRNA expression showed that miR-21-3p increased in mutated versus wild-type DTs, while miR-197-3p was decreased. The mRNA expression of Tetraspanin3 and Serpin family A member 3, miR-21-3p targets, and L1 Cell Adhesion Molecule, miR-197-3p target, was also evaluated. CTNNB1 mutations associated to miRNA dysregulation could help histological diagnosis of sporadic DTs and could affect the genesis and the progression of this disease.

2017-05-01 | GSE89687 | GEO

Effect of depletion of FAP on gene expression in ovarian cancer cell OVCAR8

Project description:To investigate the effcet of FAP KD in ovarian cancer cells

2023-09-20 | GSE201244 | GEO

RNA-seq of Sting overexpressing orthotopic pancreas tumors

Project description:RNA-seq of Sting overexpressing orthotopic pancreas tumors

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Transcription profiling of pancreas from patients suffering cancer (malignant tumors) and controls (benign tumors)

Project description:Comparison of expression profiling of pancreas from patients suffering cancer (malignant tumors) and controls (benign tumors).

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Gene Expression Changes in the Duodenal Adenoma-Carcinoma Sequence in Familial Adenomatous Polyposis (FAP)

Project description:Duodenal cancer is a leading cause of death in patients with FAP after colectomy. While cancer risk is up to 36% in Spigelman Stage IV patients, a significant proportion of cases occur in lower stage patients. Genome wide interrogation of APC-deficient mice revealed candidate biomarkers whose altered expression accompanied the evolution of small intestinal neoplasia. To date, no similar investigations have been pursued in FAP patients. In this study, a genome-wide transcriptional analysis of duodenal specimens from FAP patients was performed in order to describe changes occurring in the duodenal adenoma-carcinoma sequence in FAP

2018-02-27 | GSE111156 | GEO

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