Pigment epithelium–derived factor promotes peritoneal dissemination of ovarian cancer through induction of immunosuppressive macrophages
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PROVIDER: PRJNA830697 | ENA |
REPOSITORIES: ENA
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Project description:Peritoneal dissemination of ovarian cancer (OC) correlates with poor prognosis, but the mechanisms underlying the escape of OC cells from the intraperitoneal immune system have remained unknown. We here identify pigment epithelium–derived factor (PEDF) as a regulator of OC cell dissemination, which functions through induction of CD206+ IL-10–producing macrophages. High PEDF gene expression was associated with poor prognosis in OC patients. Concentrations of PEDF in ascites and serum were significantly higher in OC patients than those with more benign tumors and correlated with early recurrence of OC patients, suggesting that PEDF might serve as a prognostic biomarker. Bromodomain and extraterminal (BET) inhibitors were found to reduce PEDF expression and limit both OC cell survival and CD206+ macrophage induction in the peritoneal cavity. Our results thus implicate PEDF as a driver of OC dissemination and identify a BET protein–PEDF–IL-10 axis as a promising therapeutic target for OC.
2022-04-25 | GSE201275 | GEO
Project description: Not available
| S-EPMC9440245 | biostudies-literature
Project description:Objective Cancer immunotherapy aims to unleash the immune system's potential against cancer cells, providing sustained relief for tumors responsive to immune checkpoint inhibitors (ICIs). While promising in gastric cancer (GC) trials, the efficacy of ICIs diminishes in the context of peritoneal dissemination. Our objective is to identify strategies to enhance the impact of ICI treatment specifically for cases involving peritoneal dissemination in GC. Design The therapeutic efficacy of anti-PD1, CTLA4 treatment alone, or in combination, was assessed using the YTN16 peritoneal dissemination tumor model mice. Peritoneum and peritoneal exudate cells were collected for subsequent analysis. Immunohistochemical staining, flow cytometry, and bulk RNA-sequence analyses were conducted to evaluate the tumor microenvironment (TME). A JAK inhibitor (JAKi) was introduced based on the pathway analysis results. Results Anti-PD1 and anti-CTLA4 combination treatment (dual ICI treatment) demonstrated therapeutic efficacy in certain mice, primarily mediated by CD8+ T cells. However, in mice resistant to dual ICI treatment, even with CD8+ T cell infiltration, most of the T cells exhibited exhaustion phenotype. Notably, resistant tumors displayed abnormal activation of the JAK-STAT pathway compared to the untreated group, with observed infiltration of macrophages, neutrophils, and Tregs in the TME. The concurrent administration of JAKi rescued CD8+ T cells function and reshaped the immunosuppressive TME, resulting in enhanced efficacy of the dual ICI treatment. Conclusion Dual ICI treatment exerts its anti-tumor effects by increasing tumor- specific CD8+ T cell infiltration, and the addition of JAKi further improves ICI resistant by reshaping the immunosuppressive TME.
2024-05-28 | GSE250238 | GEO
Project description:This is the proteomic analysis data of bovine retinal pigment epithelium cell lysate subjected to cryo-EM study.
2023-01-02 | PXD037186 | Pride
Project description:BACKGROUND & AIMS: The mechanisms of peritoneal dissemination in pancreatic ductal adenocarcinoma (PDAC) remain unclear partly owing to the lack of patient-derived models that recapitulate this process. This study aimed to establish an orthotopic model of PDAC peritoneal dissemination and to uncover the transcriptional and regulatory programs underlying this process. METHODS: Organoids were established from primary pancreatic tumors and malignant effusions of patients with PDAC and orthotopically transplanted into the pancreas of immunodeficient mice to generate patient-derived orthotopic xenograft (PDOX) models. Subsequently, the organoids were rederived from pancreatic and peritoneal lesions of a representative model (PDOX12) and orthotopically reimplanted to assess the dissemination capacity. Single-nucleus RNA sequencing (snRNA-seq) and single-cell ATAC sequencing (scATAC-seq) were performed to analyze the tumors from these models. RESULTS: The organoids that were derived from malignant effusions reproducibly generated peritoneal metastases after orthotopic implantation. To dissect this process more precisely, we focused on one representative model (PDOX12) and rederived organoids from its pancreatic and peritoneal lesions. These organoids generated matched PDOX models that differed only in dissemination potential when reimplanted orthotopically. The results of snRNA-seq revealed a distinct subpopulation enriched in the high-dissemination model, which was characterized by the coordinated activation of genes involved in cytoskeletal dynamics, extracellular matrix remodeling, and plasticity-related signaling—suggesting a dissemination-primed state. Integration with scATAC-seq identified STAT3, SMAD3, and SOX2 as potential upstream regulators of this gene program. CONCLUSIONS: This study established PDOX models that isolate the peritoneal dissemination phenotype and reveal the transcriptional and regulatory programs driving this process.
2026-03-25 | GSE318413 | GEO
Project description:BACKGROUND & AIMS: The mechanisms of peritoneal dissemination in pancreatic ductal adenocarcinoma (PDAC) remain unclear partly owing to the lack of patient-derived models that recapitulate this process. This study aimed to establish an orthotopic model of PDAC peritoneal dissemination and to uncover the transcriptional and regulatory programs underlying this process. METHODS: Organoids were established from primary pancreatic tumors and malignant effusions of patients with PDAC and orthotopically transplanted into the pancreas of immunodeficient mice to generate patient-derived orthotopic xenograft (PDOX) models. Subsequently, the organoids were rederived from pancreatic and peritoneal lesions of a representative model (PDOX12) and orthotopically reimplanted to assess the dissemination capacity. Single-nucleus RNA sequencing (snRNA-seq) and single-cell ATAC sequencing (scATAC-seq) were performed to analyze the tumors from these models. RESULTS: The organoids that were derived from malignant effusions reproducibly generated peritoneal metastases after orthotopic implantation. To dissect this process more precisely, we focused on one representative model (PDOX12) and rederived organoids from its pancreatic and peritoneal lesions. These organoids generated matched PDOX models that differed only in dissemination potential when reimplanted orthotopically. The results of snRNA-seq revealed a distinct subpopulation enriched in the high-dissemination model, which was characterized by the coordinated activation of genes involved in cytoskeletal dynamics, extracellular matrix remodeling, and plasticity-related signaling—suggesting a dissemination-primed state. Integration with scATAC-seq identified STAT3, SMAD3, and SOX2 as potential upstream regulators of this gene program. CONCLUSIONS: This study established PDOX models that isolate the peritoneal dissemination phenotype and reveal the transcriptional and regulatory programs driving this process.
2026-03-25 | GSE318412 | GEO
Project description:BACKGROUND & AIMS: The mechanisms of peritoneal dissemination in pancreatic ductal adenocarcinoma (PDAC) remain unclear partly owing to the lack of patient-derived models that recapitulate this process. This study aimed to establish an orthotopic model of PDAC peritoneal dissemination and to uncover the transcriptional and regulatory programs underlying this process. METHODS: Organoids were established from primary pancreatic tumors and malignant effusions of patients with PDAC and orthotopically transplanted into the pancreas of immunodeficient mice to generate patient-derived orthotopic xenograft (PDOX) models. Subsequently, the organoids were rederived from pancreatic and peritoneal lesions of a representative model (PDOX12) and orthotopically reimplanted to assess the dissemination capacity. Single-nucleus RNA sequencing (snRNA-seq) and single-cell ATAC sequencing (scATAC-seq) were performed to analyze the tumors from these models. RESULTS: The organoids that were derived from malignant effusions reproducibly generated peritoneal metastases after orthotopic implantation. To dissect this process more precisely, we focused on one representative model (PDOX12) and rederived organoids from its pancreatic and peritoneal lesions. These organoids generated matched PDOX models that differed only in dissemination potential when reimplanted orthotopically. The results of snRNA-seq revealed a distinct subpopulation enriched in the high-dissemination model, which was characterized by the coordinated activation of genes involved in cytoskeletal dynamics, extracellular matrix remodeling, and plasticity-related signaling—suggesting a dissemination-primed state. Integration with scATAC-seq identified STAT3, SMAD3, and SOX2 as potential upstream regulators of this gene program. CONCLUSIONS: This study established PDOX models that isolate the peritoneal dissemination phenotype and reveal the transcriptional and regulatory programs driving this process.
2026-03-25 | GSE318411 | GEO
Project description:To evaluate the effect of oxidative stress on transcript localization in the retinal pigment epithelium (RPE), we performed poly-A RNA sequencing on nuclear and cytoplasmic fractions from induced pluripotent stem cell-derived retinal pigment epithelium (iPSC-RPE) cells exposed to hydrogen peroxide, as well as untreated controls.
2022-06-23 | GSE158909 | GEO
Project description:We show that Retinal pigment epithelium (RPE) secreted-factor, pigment epithelium derived factor (PEDF) secreted/derived from primary or iPSC-derived retinal pigment epithelium (RPE)RPE, dramatically inhibitsed the cell growth of iPSCs. PEDF was detected abundantly in culture supernatant media of primary and iPSC-derived RPE. We examined the gene expression in primary RPE and iPS-derived RPE. Two samples: RPE derived from 253G1 iPSC, Primary RPE.
2013-01-03 | E-GEOD-43257 | biostudies-arrayexpress
Project description:Day-night rhythm in murine retinal pigment epithelium
| PRJNA564263 | ENA