Homo sapiens
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-62518
PROVIDER: PRJNA264321 | ENA |
REPOSITORIES: ENA
Similar Datasets
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:Adipose tissue (AT) contains mesenchymal stromal cells (MSC) in stages of commitment to becoming specialized tissue cells, including adipocytes and fibroblasts, and immune cells which support tissue homeostasis. How MSC and immune cells interact during infection is poorly understood. We show that during intestinal helminth infection MSC in mesenteric AT (mAT) become enriched in non-differentiated progenitor cells. This is accompanied by MSC-intrinsic metabolic reprogramming supporting increased secretion of extracellular matrix (ECM), IL-33, and TSLP. In parallel, Th2 resident memory (Th2RM) cells populate the mAT and persist after infection is resolved. These cells express Areg, TGFβ and IL-5, and are necessary to promote infection induced changes within mAT, including MSC reprogramming and tissue eosinophilia. In turn, IL-33 and TSLP from MSC facilitate Th2RM activation and maintenance. Our findings link Th2RM cells to mAT remodeling during intestinal infection, underscoring the reciprocal dependence of stroma and resident immune cells for lasting tissue immunity.
2022-08-17 | GSE186160 | GEO
Project description:Molecular mechanisms underlying the cancer stroma in metastasis is largely unknown. Here we show that cancer-associated fibroblasts (CAFs) produce high levels of IL-33 that acted on tumor-associated macrophages (TAMs) to induce the M1 to M2 transition. Genome profiling of metastasis-related genes in the IL-33-stimulated TAMs showed a > 200-fold increase of metalloproteinase 9 (MMP9). Signaling analysis demonstrated the IL-33-ST2-NFkB-MMP9-laminin pathway that mediates cancer metastasis. In mouse and human fibroblast-rich pancreatic cancers, genetic deletion of IL-33, ST2 and MMP9 markedly blocked metastasis. Pharmacological inhibition of NFkB and MMP9 also blocked cancer metastasis. Deletion of IL-33, ST2 and MMP9 restored laminin, a key basement membrane component associated to tumor microvessels. Together, our data provide novel mechanistic insights on the IL-33-NFkB-MMP9-laminin axis that mediates the CAF-TAM-committed cancer metastasis. Thus, targeting the CAF-TAM-vessel interaction provides an outstanding therapeutic opportunity for cancer treatment.
2018-11-30 | GSE97657 | GEO
Project description:Interleukin-25 and group 2 innate lymphoid cells (ILC2s) defend the host against intestinal helminth infection, and are associated with inappropriate allergic reactions. Recently, it was reported that IL-33-activated ILC2s augment protective tissue-specific pancreatic cancer immunity. Here we show a diametrically opposite role for intestinal IL-25-activated ILC2s where they create an innate cancer-permissive microenvironment. Colorectal cancer (CRC) patients with higher tumor IL25 expression have reduced survival, and increased IL-25 Rexpressing tumor-resident ILC2s and myeloid-derived suppressor cells (MDSCs) associated with impaired anti-tumor responses. Ablation of IL-25-signalling reduced tumors, virtually doubling life-expectancy in an Apc-mutation-driven model of spontaneous intestinal tumorigenesis. Mechanistically, IL-25 promotes tumor ILC2s, which sustain MDSCs to suppress anti-tumor immunity. Therapeutic blockade of IL-25-signalling decreased ILC2s, MDSCs and adenoma/adenocarcinoma, while increasing anti-tumor IFNg and adaptive T cell immunity. Thus, the roles of innate epithelium-derived cytokines IL-25 and IL-33, and ILC2s in cancer cannot be generalized, and instead offer differential pathways for therapeutic intervention.
2022-04-20 | GSE199113 | GEO
Project description:Trichinella spiralis is a highly destructive parasitic nematode that invades and destroys intestinal epithelial cells, injures many different tissues during its migratory phase, and occupies and transforms myotubes during the final phase of its life cycle. Mice deficient in the IL-1 family receptor for the DAMP, IL-33 (called ST2), display reduced intestinal Th2 responses and impaired mast cell activation. IL-33 was constitutively expressed in intestinal epithelial cells, where it became concentrated in nuclei within 2 days of infection. Nuclear localization was an innate response to infection that occurred in intestinal regions where worms were actively migrating. We isolated intestinal epithelial cells from uninfected mice (cytoplasmic IL-33) and mice at 2 days post-infection (nuclear IL-33) to compare global expression profiles. We used microarrays to characterize the global gene expression that occurs in intestinal epithelial cells following T. spiralis-induced nuclear translocation of IL-33. Intestinal epithelial cells were isolated from Rag2-/- mice at day zero (uninfected) or two days post-infection with T. ispiralis for RNA extraction and hybridization on Affymetrix microarrays.
2015-03-28 | E-GEOD-67365 | biostudies-arrayexpress
Project description:Trichinella spiralis is a highly destructive parasitic nematode that invades and destroys intestinal epithelial cells, injures many different tissues during its migratory phase, and occupies and transforms myotubes during the final phase of its life cycle. Mice deficient in the IL-1 family receptor for the DAMP, IL-33 (called ST2), display reduced intestinal Th2 responses and impaired mast cell activation. IL-33 was constitutively expressed in intestinal epithelial cells, where it became concentrated in nuclei within 2 days of infection. Nuclear localization was an innate response to infection that occurred in intestinal regions where worms were actively migrating. We isolated intestinal epithelial cells from uninfected mice (cytoplasmic IL-33) and mice at 2 days post-infection (nuclear IL-33) to compare global expression profiles. We used microarrays to characterize the global gene expression that occurs in intestinal epithelial cells following T. spiralis-induced nuclear translocation of IL-33.
2015-03-28 | GSE67365 | GEO
Project description:APCmin/+ mice develop spontaneous gastrointestinal polyposis due to a dominantly inhereited germline loss-of-function mutation in the tumor suppressor adenomatous polyposis coli (APC). Changes in intestinal immune activity have been documented to occur prior to the development of fulminate polyposis. Such changes are thought to contribute to disease development. We used microarrays to describe the changing intestinal transcriptional landscape in APCmin/+ mice. Whole transcriptome profiling from polypotic and nonpolypotic intestinal sections of APC/min+ mice were examined in the early stages of disease, and compared to normal intestinal sections from littermate matched wildtype B6 mice.
2013-08-20 | GSE49970 | GEO
Project description:The systemic metabolic shifts that occur during aging and the local metabolic alterations of a tumor, its stroma and their communication cooperate to establish a unique tumor microenvironment (TME) that fosters cancer progression. Here, we show that methylmalonic acid (MMA), an aging-increased oncometabolite that is also produced by aggressive cancer cells, activates fibroblasts in the TME and stimulates the release of extracellular vesicles (EVs) that drive cancer progression, drug resistance and metastasis. The cancer-associated fibroblast (CAF)-released EV cargo is modified as a result of reactive oxygen species (ROS) generation and activation of the canonical and noncanonical TGFβ signaling pathways in CAFs. EV-associated IL-6 functions as a stroma-tumor messenger that activates the JAK/STAT3 and TGFβ signaling pathways in tumor cells and promote an epithelial-to-mesenchymal transition (EMT) and drug resistance in vitro, and metastatic progression in vivo. Our findings reveal the role of MMA in the activation of CAFs to drive metastatic reprogramming, unveiling multiple potential therapeutic avenues to target MMA at the nexus of aging, the tumor microenvironment and metastasis.
2022-10-04 | GSE190929 | GEO
Project description:An interactive tumor microenvironment with different stromal cell types is necessary for supporting cancer stemness. Cancers with dense fibrotic stroma such as intrahepatic cholangiocarcinoma (ICC) are often highly aggressive and chemotherapy resistance. Here, we show that cancer associated fibroblasts (CAF) greatly enhances the capacity of blood CD33+ myeloid-derived suppressor cells (MDSCs) to promote stem-like properties in ICC cells and tumor growth via paracrine signaling. Mechanistically, CAF mediates hyperactivated 5-LO pathway in CD33+ MDSCs via secretion of IL-6 and IL-33, resulting in overproduction of LTB4, which acts on BLT2 to promote cancer stemness via Akt-mTOR signaling. hyperactivated 5-LO pathway are observed in tumor-infiltrating CD33+ MDSCs compared with blood counterparts from the same ICC patients. Moreover, BLT2 blockade augments chemotherapeutic efficacy in ICC PDX models. Thus, our study reveals a previously unrecognized stromal cell network in which CAF educate myeloid cells to shape the optimal supportive microenvironment for the aggressive nature of ICC.
2022-01-01 | GSE158755 | GEO