ArticleCells2021
The P2X7 Receptor Stimulates IL-6 Release from Pancreatic Stellate Cells and Tocilizumab Prevents Activation of STAT3 in Pancreatic Cancer Cells.
Article in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed, 34 citations in OpenAlex.
- Calcitriol, the active form of vitamin D, induces cell death and purinergic signaling modulation in cutaneous melanoma cells.Medical oncology (Northwood, London, England) · 2026Article
- Methodological guidelines for P2X receptor assays and data interpretation.Cell death & disease · 2026Review
- pH-Dependent Microenvironmental Ionic Signaling in Pancreatic Ductal Adenocarcinoma.Acta physiologica (Oxford, England) · 2026Review
- Glioblastoma pathophysiology: roles of aging driven changes in STAT3 interactions with NF-κB dimer components in the modulation of the mitochondrial melatonergic pathway and night-time inflammation resolution.Exploration of targeted anti-tumor therapy · 2026Review
- P2X7 receptors: a bibliometric review from 2002 to 2023.Purinergic signalling · 2025Review
- Functional role of P2X7 purinergic receptor in cancer and cancer-related pain.Purinergic signalling · 2025Review
- Inflammation, microbiota, and pancreatic cancer.Cancer cell international · 2025Review
- Targeting Triple NK Cell Suppression Mechanisms: A Comprehensive Review of Biomarkers in Pancreatic Cancer Therapy.International journal of molecular sciences · 2025Review
- Role of P2X7 receptor in the progression and clinicopathological characteristics of gastric cancer.Scientific reports · 2024Article
- Human P2X7 receptor variants Gly150Arg and Arg276His polymorphisms have differential effects on risk association and cellular functions in pancreatic cancer.Cancer cell international · 2024Article
- Pancreatic stellate cells in pancreatic cancer: as potential targets for future therapy.Frontiers in oncology · 2023Review
- The shed P2X7 receptor is an index of adverse clinical outcome in COVID-19 patients.Frontiers in immunology · 2023Article
- Repurposing the Antibacterial Agents Peptide 19-4LF and Peptide 19-2.5 for Treatment of Cutaneous Leishmaniasis.Pharmaceutics · 2022Article
- Review
- Resistance to Gemcitabine in Pancreatic Ductal Adenocarcinoma: A Physiopathologic and Pharmacologic Review.Cancers · 2022Review
- Current Trends and Research Hotspots in Pancreatic Stellate Cells: A Bibliometric Study.Frontiers in oncology · 2022Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Pancreatic stellate cells (PSCs) are important pancreatic fibrogenic cells that interact with pancreatic cancer cells to promote the progression of pancreatic ductal adenocarcinoma (PDAC). In the tumor microenvironment (TME), several factors such as cytokines and nucleotides contribute to this interplay. Our aim was to investigate whether there is an interaction between IL-6 and nucleotide signaling, in particular, that mediated by the ATP-sensing P2X7 receptor (P2X7R). Using human cell lines of PSCs and cancer cells, as well as primary PSCs from mice, we show that ATP is released from both PSCs and cancer cells in response to mechanical and metabolic cues that may occur in the TME, and thus activate the P2X7R. Functional studies using P2X7R agonists and inhibitors show that the receptor is involved in PSC proliferation, collagen secretion and IL-6 secretion and it promotes cancer cell migration in a human PSC-cancer cell co-culture. Moreover, conditioned media from P2X7R-stimulated PSCs activated the JAK/STAT3 signaling pathway in cancer cells. The monoclonal antibody inhibiting the IL-6 receptor, Tocilizumab, inhibited this signaling. In conclusion, we show an important mechanism between PSC-cancer cell interaction involving ATP and IL-6, activating P2X7 and IL-6 receptors, respectively, both potential therapeutic targets in PDAC.
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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.