Effect of mast cells on the phenotype of breast cancer cells
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ABSTRACT:
PROVIDER: PRJNA580265 | ENA |
REPOSITORIES: ENA
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Project description:To understand the mechanisms by which mast cells affect the features of breast cancer cells, we collected spontaneous mammary tumors from MMTV-PyMT mice, C57BL/6 wild type or back-crossed with Wsh mice which lack mast cells. Gene expression profiling was performed to select the genes which are differentially expressed in the presence or absence of mast cells.
2020-10-29 | GSE139568 | GEO
Project description:Mast cells, activated by antigen via the high affinity receptor for IgE (FcεRI), release an array of pro-inflammatory mediators that contribute to allergic disorders such as asthma and anaphylaxis. The KIT ligand, stem cell factor (SCF), is critical for mast cell expansion, differentiation and survival, and, under acute conditions, enhances mast cell activation. However, extended SCF exposure in vivo conversely protects against fatal antigen-mediated anaphylaxis. In investigating this dichotomy, we identified a novel mode of regulation of the mast cell activation phenotype through SCF-mediated programming. We found that mouse bone marrow-derived mast cells chronically exposed to SCF displayed a marked attenuation of FcεRI-mediated degranulation and cytokine production. The hypo-responsive phenotype was not a consequence of altered signals regulating calcium flux or protein kinase C, but of ineffective cytoskeletal reorganization, with evidence implicating a down-regulation of expression of the Src kinase Hck. Collectively, these findings demonstrate a major role for SCF in the homeostatic control of mast cell activation with potential relevance to mast cell-driven disease and the development of novel approaches for the treatment of allergic disorders. Mouse bone marrow-derived mast cells were treated with IL3, IL3+IL33, or IL3+SCF. Six replicates each.
2012-05-01 | E-GEOD-35332 | biostudies-arrayexpress
Project description:Chronic rhinosinusitis (CRS) is more prevalent and severe in military Veterans with deployment-related environmental toxin exposures. The mechanisms driving this aggressive phenotype are poorly understood, and the role of mast cells remains understudied. We sought to characterize the immunophenotype of toxin-associated CRS and develop a preclinical model to investigate disease persistence. We identified a significant and selective expansion of sinus mast cells in Veterans with deployment-related exposures compared to unexposed controls, an effect most prominent in patients without nasal polyps. RNA sequencing of sinus tissue from exposed patients confirmed the upregulation of mast cell activation pathways. We also developed a murine model in which co-exposure to burn pit constituents (BPC) and an aeroallergen synergistically exacerbated sinonasal inflammation. Strikingly, mast cell accumulation persisted and continued to increase for weeks after toxin exposure ceased, a phenomenon not observed in mice challenged with allergen alone. Our findings reveal a novel mast cell-driven phenotype in toxin exposure-associated CRS. The persistent accumulation of mast cells in our preclinical model provides a potential mechanism for the chronicity of sinonasal symptoms following xenobiotic exposures, identifying mast cells as a potential therapeutic target for this emerging CRS phenotype.
2026-01-27 | GSE313186 | GEO
Project description:Mast cells accumulate in breast cancer, but there is only limited knowledge of how they impact on breast cancer growth. Here we show that tryptase, a major compound stored in mast cell secretory granules, has profound effects on breast cancer cell morphology and growth, the latter by a combination of anti-proliferative and pro-apoptotic effects. Mechanistically, we show that tryptase is taken up by breast cancer cells, and enters their nuclei. Further, tryptase was shown to cause major effects on chromatin organization, and to induce truncation of core histone-3 (H3). H3 truncation was accompanied by reduced levels of epigenetic marks associated with H3. In vivo, tryptase-positive mast cells were found in PyMT breast cancer tumours and in human triple negative breast cancer, and a proliferation clearance zone was seen in the vicinity of tryptase-positive mast cells. It was also observed that mast cells were activated to a higher extent in breast cancer tumours than in healthy tissue. Finally, ATAC-seq analysis revealed that tryptase affected chromatin accessibility at regions of the genome associated with genes known to influence breast cancer growth. Altogether, the present study introduces a mechanism for how mast cell tryptase can regulate breast cancer cell growth.
2025-12-03 | GSE307724 | GEO
Project description:Mast cells are known to accumulate in breast cancer, but there is only limited knowledge of how they may impact on breast cancer growth. Tryptase is one of the major compounds stored in the mast cell secretory granules, and here we investigated whether tryptase can have an influence on breast cancer cells. Our findings reveal that tryptase has profound effects on breast cancer cell morphology and that tryptase has a negative impact on the growth of breast cancer cells, the latter by a combination of anti-proliferative and pro-apoptotic effects. Mechanistically, we show that tryptase is taken up by breast cancer cells, and enters their nuclei. Further, tryptase was shown to cause major effects on chromatin organization, and to induce truncation of core histone 3 (H3). H3 truncation was accompanied by reduced levels of epigenetic marks associated with H3. In vivo, tryptase-positive mast cells were found in PyMT breast cancer tumors in mice, and a proliferation clearance zone was seen in the vicinity of tryptase-positive mast cells. Similarly, a proliferation clearance zone was observed in the vicinity of tryptase-positive mast cells in human triple negative breast cancer. It was also observed that mast cells were activated to a higher extent in breast cancer tumors than in healthy breast tissue. In agreement with an anti-proliferative impact of tryptase on breast cancer, ATAC-seq analysis revealed that tryptase affected chromatin accessibility at several regions of the genome associated with genes known to influence breast cancer growth. Altogether, the present study introduces a mechanism for how mast cell tryptase can regulate breast cancer cell growth.
2025-09-17 | GSE308338 | GEO
Project description:Mast cells, activated by antigen via the high affinity receptor for IgE (FcεRI), release an array of pro-inflammatory mediators that contribute to allergic disorders such as asthma and anaphylaxis. The KIT ligand, stem cell factor (SCF), is critical for mast cell expansion, differentiation and survival, and, under acute conditions, enhances mast cell activation. However, extended SCF exposure in vivo conversely protects against fatal antigen-mediated anaphylaxis. In investigating this dichotomy, we identified a novel mode of regulation of the mast cell activation phenotype through SCF-mediated programming. We found that mouse bone marrow-derived mast cells chronically exposed to SCF displayed a marked attenuation of FcεRI-mediated degranulation and cytokine production. The hypo-responsive phenotype was not a consequence of altered signals regulating calcium flux or protein kinase C, but of ineffective cytoskeletal reorganization, with evidence implicating a down-regulation of expression of the Src kinase Hck. Collectively, these findings demonstrate a major role for SCF in the homeostatic control of mast cell activation with potential relevance to mast cell-driven disease and the development of novel approaches for the treatment of allergic disorders.
2012-05-02 | GSE35332 | GEO
Project description:Interleukin-33 (IL-33) is elevated in afflicted tissues of patients with mast cell-dependent chronic allergic diseases. Based on its acute effects on mouse mast cells (MCs), IL-33 is thought to play a role in the pathogenesis of allergic disease through MC activation. However, the manifestations of chronic IL-33 exposure on human MC function, which best reflect the conditions associated with chronic allergic disease, are unknown. We now find that long-term exposure of human and mouse MCs to IL-33 results in a substantial reduction of MC activation in response to antigen. This reduction required >72 h exposure to IL-33 for onset and 1-2 wk for reversion following IL-33 removal. This hypo-responsive phenotype was determined to be a consequence of MyD88-dependent attenuation of signaling processes necessary for MC activation including antigen-mediated calcium mobilization and cytoskeletal reorganization; potentially as a consequence of down-regulation of the expression of PLCg1 and Hck. These findings suggest that IL-33 may play a protective, rather than a causative role in MC activation under chronic conditions and, furthermore, reveal regulated plasticity in the MC activation phenotype. The ability to down-regulate MC activation in this manner may provide alternative approaches for treatment of MC-driven disease. Mouse bone marrow-derived mast cells treated with IL3 or IL3+IL33. 6 replicates each.
2013-02-06 | E-GEOD-39382 | biostudies-arrayexpress
Project description:ZEB1-regulated inflammatory phenotype in breast cancer cells
| PRJNA350678 | ENA
Project description:Microenvironment-based alterations in mast cell phenotypes influence the susceptibility to anaphylaxis, yet the mechanisms underlying proper maturation of mast cells toward an anaphylaxis-sensitive phenotype are incompletely understood. Here we report that PLA2G3, a mammalian homolog of anaphylactic bee venom phospholipase A2, regulates this process. PLA2G3 secreted from mast cells is coupled with fibroblastic lipocalin-type PGD2 synthase (L-PGDS) to provide PGD2, which facilitates mast cell maturation via PGD2 receptor (DP1). Mice lacking PLA2G3, L-PGDS or DP1, mast cell-deficient mice reconstituted with PLA2G3- or DP1-null mast cells, or mast cells cocultured with L-PGDS-ablated fibroblasts exhibited impaired mast cell maturation and anaphylaxis. Thus, we describe a lipid-driven PLA2G3-L-PGDS-DP1 loop that drives mast cell maturation.
2013-03-09 | GSE44980 | GEO
Project description:The difference between intraepithelial mast cells and lamina propria mast cells
| PRJNA981202 | ENA