ArticleEMBO reports2020
High-grade mesenchymal pancreatic ductal adenocarcinoma drives stromal deactivation through CSF-1.
Article in EMBO reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 39 citations in OpenAlex.
- Trial
- Estrogen Production in Pancreatic Cancer Shapes a Tumor-Suppressive Stromal Microenvironment.Cancer research · 2026Article
- Dynamics of inflammatory signals within the tumor microenvironment.World journal of experimental medicine · 2025Review
- Targeting Triple NK Cell Suppression Mechanisms: A Comprehensive Review of Biomarkers in Pancreatic Cancer Therapy.International journal of molecular sciences · 2025Review
- Innate and adaptive immune-directed tumour microenvironment in pancreatic ductal adenocarcinoma.Frontiers in immunology · 2024Review
- Cancer-associated fibroblast-related prognostic signature predicts prognosis and immunotherapy response in pancreatic adenocarcinoma based on single-cell and bulk RNA-sequencing.Scientific reports · 2023Article
- Cell-selective proteomics segregates pancreatic cancer subtypes by extracellular proteins in tumors and circulation.Nature communications · 2023Article
- Rapid cancer cell perineural invasion utilizes amoeboid migration.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The Extracellular Matrix: Its Composition, Function, Remodeling, and Role in Tumorigenesis.Biomimetics (Basel, Switzerland) · 2023Review
- Single-cell profiling to explore pancreatic cancer heterogeneity, plasticity and response to therapy.Nature cancer · 2023Review
- Proteome alterations during clonal isolation of established human pancreatic cancer cell lines.Cellular and molecular life sciences : CMLS · 2022Article
- Disease-related protein co-expression networks are associated with the prognosis of resectable node-positive pancreatic ductal adenocarcinoma.Scientific reports · 2022Article
- Heterogeneity of Cancer-Associated Fibroblasts and the Tumor Immune Microenvironment in Pancreatic Cancer.Cancers · 2022Review
- Subtypes in pancreatic ductal adenocarcinoma based on niche factor dependency show distinct drug treatment responses.Journal of experimental & clinical cancer research : CR · 2022Article
- Selective multi-kinase inhibition sensitizes mesenchymal pancreatic cancer to immune checkpoint blockade by remodeling the tumor microenvironment.Nature cancer · 2022Article
- Glucose metabolism and tumour microenvironment in pancreatic cancer: A key link in cancer progression.Frontiers in immunology · 2022Review
- Bioengineered 3D models of human pancreatic cancer recapitulate in vivo tumour biology.Nature communications · 2021Article
- The receptor of the colony-stimulating factor-1 (CSF-1R) is a novel prognostic factor and therapeutic target in follicular lymphoma.Leukemia · 2021Article
- The molecular biology of pancreatic adenocarcinoma: translational challenges and clinical perspectives.Signal transduction and targeted therapy · 2021Review
- Review
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Authors and funding
20 authors at 4 institutions in 2 countries.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is characterized by an abundance of stroma. Multiple molecular classification efforts have identified a mesenchymal tumor subtype that is consistently characterized by high-grade growth and poor clinical outcome. The relation between PDAC stroma and tumor subtypes is still unclear. Here, we aimed to identify how PDAC cells instruct the main cellular component of stroma, the pancreatic stellate cells (PSCs). We found in primary tissue that high-grade PDAC had reduced collagen deposition compared to low-grade PDAC. Xenografts and organotypic co-cultures established from mesenchymal-like PDAC cells featured reduced collagen and activated PSC content. Medium transfer experiments using a large set of PDAC cell lines revealed that mesenchymal-like PDAC cells consistently downregulated ACTA2 and COL1A1 expression in PSCs and reduced proliferation. We identified colony-stimulating factor 1 as the mesenchymal PDAC-derived ligand that deactivates PSCs, and inhibition of its receptor CSF1R was able to counteract this effect. In conclusion, high-grade PDAC features stroma that is low in collagen and activated PSC content, and targeting CSF1R offers direct options to maintain a tumor-restricting microenvironment.
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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.