ArticleOncotarget2016
Pancreatic stellate cell secreted IL-6 stimulates STAT3 dependent invasiveness of pancreatic intraepithelial neoplasia and cancer cells.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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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.
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Who cites it
71 citing papers in PubMed, 112 citations in OpenAlex.
- Trial
- Article
- Heterocellular crosstalk and architecture of the pancreatic tumour microenvironment.Nature reviews. Cancer · 2026Review
- Crucial role of IL-6, IL-8, IL-11 and leptin in tumor microenvironment in a group of patients with GEP-NETs- crosstalk between inflammation and cancer.Frontiers in endocrinology · 2026Article
- Pancreatic cancer-associated myofibroblasts: a review.International journal of biological sciences · 2026Review
- The Vitamin D3 Analog Calcipotriol Attenuates Pancreatic Cancer Malignancy via Downregulating Thrombospondin 1 in Pancreatic Stellate Cells.Mediators of inflammation · 2026Article
- CAR-Macrophage Cell Therapy: A New Era of Hope for Pancreatic Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Review
- Review
- CCN1 Enhances Tumor Immunosuppression through Collagen-Mediated Chemokine Secretion in Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Serum Mac2-binding protein glycosylated isomer (M2BPGi) as a prognostic biomarker in pancreatic ductal adenocarcinoma: iCAFs-derived M2BPGi drives tumor invasion.Journal of gastroenterology · 2025Article
- The role of inflammatory factors in the tumor microenvironment of pancreatic cancer.Frontiers in immunology · 2025Review
- Role of Interleukins in Pancreatic Cancer: A Literature Review.Journal of gastrointestinal cancer · 2024Review
- Pancreatic stellate cells and the interleukin family: Linking fibrosis and immunity to pancreatic ductal adenocarcinoma (Review).Molecular medicine reports · 2024Review
- The cross-talk between the macro and micro-environment in precursor lesions of pancreatic cancer leads to new and promising circulating biomarkers.Journal of experimental & clinical cancer research : CR · 2024Review
- Interleukin-1α as a Potential Prognostic Biomarker in Pancreatic Cancer.Biomedicines · 2024Article
- Tumor Stroma as a Therapeutic Target for Pancreatic Ductal Adenocarcinoma.Biomolecules & therapeutics · 2024Review
- Single-cell RNA sequencing to explore cancer-associated fibroblasts heterogeneity: "Single" vision for "heterogeneous" environment.Cell proliferation · 2024Review
- Role of STAT3 in pancreatic cancer.Exploration of targeted anti-tumor therapy · 2024Review
- Regnase-1 downregulation promotes pancreatic cancer through myeloid-derived suppressor cell-mediated evasion of anticancer immunity.Journal of experimental & clinical cancer research : CR · 2023Article
- SHP2 regulates adipose maintenance and adipocyte-pancreatic cancer cell crosstalk via PDHA1.Journal of cell communication and signaling · 2023Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a dynamic tumor supported by several stromal elements such as pancreatic stellate cells (PSC). Significant crosstalk exists between PSCs and tumor cells to stimulate oncogenic signaling and malignant progression of PDAC. However, how PSCs activate intercellular signaling in PDAC cells remains to be elucidated. We have previously shown that activated signal transducer and activator of transcription 3 (STAT3) signaling is a key component in the progression of pancreatic neoplasia. We hypothesize that PSC secreted IL-6 activates STAT3 signaling to promote PanIN progression to PDAC. Human PDAC and mouse PanIN cells were treated with PSC-conditioned media (PSC-CM), and phospho- and total-STAT3 levels by immunoblot analysis were determined. IL-6 was quantified in PSC-CM and cell invasion and colony formation assays were performed in the presence or absence of a neutralizing IL-6 antibody and the JAK/STAT3 inhibitor AZD1480. Serum from Ptf1aCre/+;LSL-KrasG12D/+;Tgfbr2flox/flox (PKT) and LSL-KrasG12D/+; Trp53R172H/+; Pdx1Cre/+ (KPC) mice demonstrated increased levels of IL-6 compared to serum from non-PDAC bearing KC and PK mice. PSC secreted IL-6 activated STAT3 signaling in noninvasive, precursor PanIN cells as well as PDAC cells, resulting in enhanced cell invasion and colony formation in both cell types. There was a significant positive linear correlation between IL-6 concentration and the ratio of phosphorylated STAT3/total STAT3. IL-6 neutralization or STAT3 inhibition attenuated PSC-CM induced activation of STAT3 signaling and tumorigenicity. These data provide evidence that PSCs are directly involved in promoting the progression of PanINs towards invasive carcinoma. This study demonstrates a novel role of PSC secreted IL-6 in transitioning noninvasive pancreatic precursor cells into invasive PDAC through the activation of STAT3 signaling.
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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.