ArticleCancers2019
The Hepatic Microenvironment and TRAIL-R2 Impact Outgrowth of Liver Metastases in Pancreatic Cancer after Surgical Resection.
Article in Cancers, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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The trial behind it
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Initial Site of Metastasis Influences Prognosis in Pancreatic Ductal Adenocarcinoma.Cancer medicine · 2026Article
- Review
- Review
- Review
- Serum-Free Production of Human Stem Cell-Derived Liver Spheres for Cancer Metastasis Research.Methods in molecular biology (Clifton, N.J.) · 2023Article
- C-Reactive Protein as Predictor for Infectious Complications after Robotic and Open Esophagectomies.Journal of clinical medicine · 2022Article
- Biomarkers in Liquid Biopsies for Prediction of Early Liver Metastases in Pancreatic Cancer.Cancers · 2022Article
- Thorny ground, rocky soil: Tissue-specific mechanisms of tumor dormancy and relapse.Seminars in cancer biology · 2022Review
- Review
- Regulation of Cancer Metastasis by TRAIL/Death Receptor Signaling.Biomolecules · 2021Review
- Steps in metastasis: an updated review.Medical oncology (Northwood, London, England) · 2021Review
- The current paradigm and challenges ahead for the dormancy of disseminated tumor cells.Nature cancer · 2020Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Most patients with pancreatic ductal adenocarcinoma (PDAC) undergoing curative resection relapse within months, often with liver metastases. The hepatic microenvironment determines induction and reversal of dormancy during metastasis. Both tumor growth and metastasis depend on the Tumor necrosis factor (TNF)-related apoptosis-inducing ligand-receptor 2 (TRAIL-R2). This study investigated the interplay of TRAIL-R2 and the hepatic microenvironment in liver metastases formation and the impact of surgical resection. Although TRAIL-R2-knockdown (PancTu-I shTR2) decreased local relapses and number of macroscopic liver metastases after primary tumor resection in an orthotopic PDAC model, the number of micrometastases was increased. Moreover, abdominal surgery induced liver inflammation involving activation of hepatic stellate cells (HSCs) into hepatic myofibroblasts (HMFs). In coculture with HSCs, proliferation of PancTu-I shTR2 cells was significantly lower compared to PancTu-I shCtrl cells, an effect still observed after switching coculture from HSC to HMF, mimicking surgery-mediated liver inflammation and enhancing cell proliferation. CXCL-8/IL-8 blockade diminished HSC-mediated growth inhibition in PancTu-I shTR2 cells, while Vascular Endothelial Growth Factor (VEGF) neutralization decreased HMF-mediated proliferation. Overall, this study points to an important role of TRAIL-R2 in PDAC cells in the interplay with the hepatic microenvironment during metastasis. Resection of primary PDAC seems to induce liver inflammation, which might contribute to outgrowth of liver metastases.
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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.