ArticleClinical & developmental immunology2012
Epithelial-to-mesenchymal transition in pancreatic ductal adenocarcinoma and pancreatic tumor cell lines: the role of neutrophils and neutrophil-derived elastase.
Article in Clinical & developmental immunology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 1 of them a synthesis that pooled it.
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Who cites it
75 citing papers in PubMed, 1 synthesis or guideline pooled it, 127 citations in OpenAlex.
- Prognostic significance of the neutrophil-to-lymphocyte ratio in primary liver cancer: a meta-analysis.PloS one · 2014Pooled it
- Association between albumin-related inflammatory biomarkers and breast cancer risk: A secondary analysis of NHANES 1998-2018.Medicine · 2025Observational
- Immunomodulatory Role of Propolis in Hypoxia and in the Tumor Microenvironment.Molecules (Basel, Switzerland) · 2025Review
- The relationship of Systemic Inflammatory Index with asthma in adults: A retrospective cross-sectional study.The Journal of international medical research · 2025Article
- Neutrophil Dynamics in Response to Cancer Therapies.Cancers · 2025Review
- A nomogram model based on routine serum markers for predicting the occurrence of primary cholangitis after Kasai operation for biliary atresia.Translational pediatrics · 2025Article
- Neutrophil Spatiotemporal Regulatory Networks: Dual Roles in Tumor Growth Regulation and Metastasis.Biomedicines · 2025Review
- Neutrophils in Cancer immunotherapy: friends or foes?Molecular cancer · 2024Review
- Targeting neutrophil elastase is a promising direction for future cancer treatment.Discover oncology · 2024Review
- Prognostic impact of tumor-associated neutrophils in breast cancer.International journal of clinical and experimental pathology · 2024Article
- Review
- Neutrophil Extracellular Traps Promote Metastases of Colorectal Cancers through Activation of ERK Signaling by Releasing Neutrophil Elastase.International journal of molecular sciences · 2023Article
- Pterostilbene supresses inflammation-induced melanoma metastasis by impeding neutrophil elastase-mediated thrombospondin-1 degradation.Chinese herbal medicines · 2023Article
- The value of enhanced CT features and texture-signatures in assessing the inflammatory infiltration of pancreatic ductal adenocarcinoma.Frontiers in oncology · 2023Article
- Review
- An Immunological Perspective of Circulating Tumor Cells as Diagnostic Biomarkers and Therapeutic Targets.Life (Basel, Switzerland) · 2022Review
- Polymorphonuclear Neutrophils and Tumors: Friend or Foe?Experientia supplementum (2012) · 2022Article
- Macrophage and Neutrophil Interactions in the Pancreatic Tumor Microenvironment Drive the Pathogenesis of Pancreatic Cancer.Cancers · 2021Review
- [The microarchitecture of pancreatic cancer from the point of view of the pathologist and the radiologist].Der Pathologe · 2021Review
- The presence of tumour-infiltrating neutrophils is an independent adverse prognostic feature in clear cell renal cell carcinoma.The journal of pathology. Clinical research · 2021Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is frequently associated with fibrosis and a prominent inflammatory infiltrate in the desmoplastic stroma. Moreover, in PDAC, an epithelial-to-mesenchymal transition (EMT) is observed. To explore a possible connection between the infiltrating cells, particularly the polymorphonuclear neutrophils (PMN) and the tumor cell transition, biopsies of patients with PDAC (n = 115) were analysed with regard to PMN infiltration and nuclear expression of β-catenin and of ZEB1, well-established indicators of EMT. In biopsies with a dense PMN infiltrate, a nuclear accumulation of β-catenin and of ZEB1 was observed. To address the question whether PMN could induce EMT, they were isolated from healthy donors and were cocultivated with pancreatic tumor cells grown as monolayers. Rapid dyshesion of the tumor cells was seen, most likely due to an elastase-mediated degradation of E-cadherin. In parallel, the transcription factor TWIST was upregulated, β-catenin translocated into the nucleus, ZEB1 appeared in the nucleus, and keratins were downregulated. EMT was also induced when the tumor cells were grown under conditions preventing attachment to the culture plates. Here, also in the absence of elastase, E-cadherin was downmodulated. PMN as well as prevention of adhesion induced EMT also in liver cancer cell line. In conclusion, PMN via elastase induce EMT in vitro, most likely due to the loss of cell-to-cell contact. Because in pancreatic cancers the transition to a mesenchymal phenotype coincides with the PMN infiltrate, a contribution of the inflammatory response to the induction of EMT and-by implication-to tumor progression is possible.
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