Stromal myofibroblasts drive tumorigenesis in Peutz-Jeghers Syndrome polyposis models
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB19821 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Germline mutations in LKB1 predispose to hereditary Peutz-Jeghers Syndrome (PJS), manifesting with gastrointestinal polyposis. We discovered that conditional deletion of Lkb1 in stromal fibroblasts using Fsp1-Cre leads to expansion of stromal cells and gastrointestinal polyposis in mice. Here we have investigated gene expression signatures in the Fsp1-Cre;Lkb1fl/fl mouse polyps harbouring bi-allelic deletion of Lkb1 in stromal cells together with wild-type epithelium. We provide RNA-seq gene expression data of 6 polyps, 4 adjacent gastric mucosa samples and 5 wild-type gastric mucosa samples from littermate controls. Our experiment demonstrates e.g. activated cytokine signaling and inflammatory pathways in the polyps.
2018-01-05 | E-MTAB-5549 | biostudies-arrayexpress
Project description:Progression of duodenal polyposis into cancer is an important cause of morbidity and mortality in the inherited tumour syndromes Familial Adenomatous Polyposis (FAP) and MUTYH-associated Polyposis (MAP), yet this process remains poorly understood. This study aimed to identify genes that are mutated in FAP and MAP duodenal adenomas and to characterise the cellular consequences for duodenal tumorigenesis.
2023-08-07 | GSE189035 | GEO
Project description:Pre-neoplastic stromal cells drive BRCA1-mediated breast tumorigenesis
| PRJNA730582 | ENA
Project description:This SuperSeries is composed of the following subset Series: GSE32727: EMT inducers catalyze malignant transformation of mammary epithelial cells and drive tumorigenesis towards claudin-low tumors [human] GSE32904: EMT inducers catalyze malignant transformation of mammary epithelial cells and drive tumorigenesis towards claudin-low tumors [mouse] Refer to individual Series
2012-07-23 | E-GEOD-32905 | biostudies-arrayexpress
Project description:Tumor epithelial cells develop within a microenvironment consisting of extracellular matrix, growth factors, and cytokines produced by non-epithelial stromal cells. In response to paracrine signals from tumor epithelia, stromal cells modify the microenvironment to promote tumor growth and metastasis. Here, we identify interleukin (IL)-33 as an epithelial cell-derived regulator of stromal cell activation and mediator of intestinal polyposis. IL-33 expression was elevated in the tumors and serum of colorectal cancer patients and induced in the adenomatous polyps of ApcMin/+ mutant mice. Genetic and antibody suppression of IL-33 signaling in ApcMin/+ mice inhibited proliferation, induced apoptosis, and suppressed angiogenesis in polyps, which reduced both tumor number and size. In ApcMin/+ polyps, IL-33 expression localized to tumor epithelial cells and expression of the IL-33 receptor, IL1RL1, associated with two stromal cell types, namely subepithelial myofibroblasts (SEMFs) and mast cells, whose activation was previously associated with polyposis. In vitro IL-33 stimulation of human SEMFs induced the expression of extracellular matrix components and growth factors associated with intestinal tumor progression. IL-33 deficiency reduced mast cell accumulation in ApcMin/+ polyps and expression of mast cell-derived proteases and cytokines known to promote polyposis. Together, our results suggest that IL-33 is a tumor epithelial cell-derived paracrine signal that promotes polyposis through the coordinated activation of stromal cells and the formation of a reactive stroma microenvironment. Six T-75 flasks of CCD-18Co cells were grown to 80% confluency; three were treated with rhIL-33, three were given vehicle control; cells were trypsinized and split in two--half of each flask used for sequencing and half for qPCR validation post-sequencing
2015-04-29 | E-GEOD-62518 | biostudies-arrayexpress
Project description:Tumor epithelial cells develop within a microenvironment consisting of extracellular matrix, growth factors, and cytokines produced by non-epithelial stromal cells. In response to paracrine signals from tumor epithelia, stromal cells modify the microenvironment to promote tumor growth and metastasis. Here, we identify interleukin (IL)-33 as an epithelial cell-derived regulator of stromal cell activation and mediator of intestinal polyposis. IL-33 expression was elevated in the tumors and serum of colorectal cancer patients and induced in the adenomatous polyps of ApcMin/+ mutant mice. Genetic and antibody suppression of IL-33 signaling in ApcMin/+ mice inhibited proliferation, induced apoptosis, and suppressed angiogenesis in polyps, which reduced both tumor number and size. In ApcMin/+ polyps, IL-33 expression localized to tumor epithelial cells and expression of the IL-33 receptor, IL1RL1, associated with two stromal cell types, namely subepithelial myofibroblasts (SEMFs) and mast cells, whose activation was previously associated with polyposis. In vitro IL-33 stimulation of human SEMFs induced the expression of extracellular matrix components and growth factors associated with intestinal tumor progression. IL-33 deficiency reduced mast cell accumulation in ApcMin/+ polyps and expression of mast cell-derived proteases and cytokines known to promote polyposis. Together, our results suggest that IL-33 is a tumor epithelial cell-derived paracrine signal that promotes polyposis through the coordinated activation of stromal cells and the formation of a reactive stroma microenvironment.
2015-04-29 | GSE62518 | GEO
Project description:All samples are conditioned media from primary cultured human gastric myofibroblasts, derived from either carcinoma tissue, or adjacent non cancerous tissue. In each experiment the cancer-derived myofibroblasts are compared against the non-cancer derived myofibroblasts from the same patient. All of the experiments were samples from Patient 1, except for 648, which is from Patient 2. SILAC labelling in each case is; 567 - Methionine COFRADIC; Cancer-derived = Heavy, Non-cancer = Light 575 - N-terminal COFRADIC; Cancer-derived = Heavy, Non-cancer = Light 646 - Cancer-derived = Light, Non-cancer = Heavy 647 - Non-cancer = Heavy, Non-cancer = Light (same cell line labelled twice to create a control experiment) 648 - Cancer-derived = Heavy, Non-cancer = Light
2013-06-20 | PRD000744 | Pride
Project description:Cancer-associated fibroblasts are a major component of the cancer stroma. Here we focus on gastric cancer associated myofibroblasts (CAMs). CAMs secrete factors that increase the migration, invasion and proliferation of cancer cells when compared to adjacent tissue myofibroblasts (ATMs), or normal tissue myofibroblasts (NTMs). In this study we identified and quantified the proteins secreted by normoxic (21% O2) and hypoxic (1% O2) myofibroblast cells.
2019-03-04 | PXD008104 | Pride
Project description:Igf1r signaling is required in fibroblasts to drive the formation of new alveoli, and those activities is depend upon its regulation on mechanical property of myofibroblasts via an Akt/Yap mechanism.
2021-02-11 | GSE158451 | GEO
Project description:Transparent avascular cornea providing two third refraction to the eye. Restoration of corneal transparency and clear vision in a traumatic eye involves the action of many cytokines and signaling pathways. Out of several factors, stromal keratocytes/fibroblasts (CSFs) play a central role in corneal repair and wound healing. Post trauma, keratocytes/fibroblasts produce myofibroblasts to facilitate wound repair by synthesizing and secreting large extracellular matrix components, collagens, and alpha-smooth muscle actin stress fibers. This study aimed to perform RNASeq data analysis and pathway enrichments to gain a better understanding of gene regulation in corneal fibroblasts and myofibroblasts in corneal wound repair.
2024-03-11 | GSE260476 | GEO