ArticleNeoplasia (New York, N.Y.)2016
Stromal ETS2 Regulates Chemokine Production and Immune Cell Recruitment during Acinar-to-Ductal Metaplasia.
Article in Neoplasia (New York, N.Y.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- Colorectal cancer-derived exosomal ETS2 promotes macrophage M2 polarization by transcriptionally activating PRPF4.Human cell · 2026Article
- ETS‑1/ETS‑2 transcription factors in CVD (Review).International journal of molecular medicine · 2026Review
- Prognostic Significance and Immune Correlation of CCL3 Expression in Colon Adenocarcinoma: Insights From Multidatabase Analysis.Biochemistry research international · 2026Article
- Targeting the ac4C 'Writer' NAT10 enhances pancreatic cancer immunotherapy via dual modulation of CD8+ T cells and tumor cells.Cell death & disease · 2025Article
- Machine learning-based biomarker screening for acute myeloid leukemia prognosis and therapy from diverse cell-death patterns.Scientific reports · 2024Article
- Cellular Origins and Lineage Plasticity in Cancer.Cold Spring Harbor perspectives in medicine · 2024Review
- Regulation of metaplasia and dysplasia in the stomach by the stromal microenvironment.Experimental & molecular medicine · 2024Review
- Coordinated chemokine expression defines macrophage subsets across tissues.Nature immunology · 2024Article
- STAT3 in tumor fibroblasts promotes an immunosuppressive microenvironment in pancreatic cancer.Life science alliance · 2022Article
- Biomarkers in Liquid Biopsies for Prediction of Early Liver Metastases in Pancreatic Cancer.Cancers · 2022Article
- Deep learning tools and modeling to estimate the temporal expression of cell cycle proteins from 2D still images.PLoS computational biology · 2022Article
- Machine Learning Reveals Ets2 as a Novel Target for Membranous Nephropathy Treatment and Its Role in Immune Infiltration.Frontiers in medicine · 2022Article
- The Establishment and Experimental Verification of an lncRNA-Derived CD8+ T Cell Infiltration ceRNA Network in Colorectal Cancer.Clinical Medicine Insights. Oncology · 2022Article
- An integrated model of acinar to ductal metaplasia-related N7-methyladenosine regulators predicts prognosis and immunotherapy in pancreatic carcinoma based on digital spatial profiling.Frontiers in immunology · 2022Article
- Article
- Ets-2 Propagates IL-6 Trans-Signaling Mediated Osteoclast-Like Changes in Human Rheumatoid Arthritis Synovial Fibroblast.Frontiers in immunology · 2021Article
- A Dynamic Transcriptome Map of Different Tissue Microenvironment Cells Identified During Gastric Cancer Development Using Single-Cell RNA Sequencing.Frontiers in immunology · 2021Article
- Therapeutic Potential of Targeting Stromal Crosstalk-Mediated Immune Suppression in Pancreatic Cancer.Frontiers in oncology · 2021Review
- Papillary Thyroid Carcinoma Landscape and Its Immunological Link With Hashimoto Thyroiditis at Single-Cell Resolution.Frontiers in cell and developmental biology · 2021Article
- A DNA Hypomethylating Drug Alters the Tumor Microenvironment and Improves the Effectiveness of Immune Checkpoint Inhibitors in a Mouse Model of Pancreatic Cancer.Cancer research · 2020Article
Corrections and comments
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Authors and funding
24 authors at 1 institution in 1 country.
Funding
Abstract
Preclinical studies have suggested that the pancreatic tumor microenvironment both inhibits and promotes tumor development and growth. Here we establish the role of stromal fibroblasts during acinar-to-ductal metaplasia (ADM), an initiating event in pancreatic cancer formation. The transcription factor V-Ets avian erythroblastosis virus E26 oncogene homolog 2 (ETS2) was elevated in smooth muscle actin-positive fibroblasts in the stroma of pancreatic ductal adenocarcinoma (PDAC) patient tissue samples relative to normal pancreatic controls. LSL-Kras(G12D/+); LSL-Trp53(R172H/+); Pdx-1-Cre (KPC) mice showed that ETS2 expression initially increased in fibroblasts during ADM and remained elevated through progression to PDAC. Conditional ablation of Ets-2 in pancreatic fibroblasts in a Kras(G12D)-driven mouse ADM model decreased the amount of ADM events. ADMs from fibroblast Ets-2-deleted animals had reduced epithelial cell proliferation and increased apoptosis. Surprisingly, fibroblast Ets-2 deletion significantly altered immune cell infiltration into the stroma, with an increased CD8+ T-cell population, and decreased presence of regulatory T cells (Tregs), myeloid-derived suppressor cells, and mature macrophages. The mechanism involved ETS2-dependent chemokine ligand production in fibroblasts. ETS2 directly bound to regulatory sequences for Ccl3, Ccl4, Cxcl4, Cxcl5, and Cxcl10, a group of chemokines that act as potent mediators of immune cell recruitment. These results suggest an unappreciated role for ETS2 in fibroblasts in establishing an immune-suppressive microenvironment in response to oncogenic Kras(G12D) signaling during the initial stages of tumor development.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.