Epithelial-to-Mesenchymal Transition in Pancreatic Ductal Adenocarcinoma and Pancreatic Tumor Cell Lines : The Role of Neutrophils and Neutrophil-Derived Elastase
Joint Authors
Giese, Thomas
Große-Steffen, Thomas
Longerich, Thomas
Hänsch, Gertrud Maria
Giese, Nathalia
Gaida, Matthias M.
Schirmacher, Peter
Source
Clinical and Developmental Immunology
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-11-20
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Große-Steffen, Thomas& Giese, Thomas& Giese, Nathalia& Longerich, Thomas& Schirmacher, Peter& Hänsch, Gertrud Maria…[et al.]. 2012. Epithelial-to-Mesenchymal Transition in Pancreatic Ductal Adenocarcinoma and Pancreatic Tumor Cell Lines : The Role of Neutrophils and Neutrophil-Derived Elastase. Clinical and Developmental Immunology،Vol. 2012, no. 2012, pp.1-12.
https://search.emarefa.net/detail/BIM-493275
Modern Language Association (MLA)
Große-Steffen, Thomas…[et al.]. Epithelial-to-Mesenchymal Transition in Pancreatic Ductal Adenocarcinoma and Pancreatic Tumor Cell Lines : The Role of Neutrophils and Neutrophil-Derived Elastase. Clinical and Developmental Immunology No. 2012 (2012), pp.1-12.
https://search.emarefa.net/detail/BIM-493275
American Medical Association (AMA)
Große-Steffen, Thomas& Giese, Thomas& Giese, Nathalia& Longerich, Thomas& Schirmacher, Peter& Hänsch, Gertrud Maria…[et al.]. Epithelial-to-Mesenchymal Transition in Pancreatic Ductal Adenocarcinoma and Pancreatic Tumor Cell Lines : The Role of Neutrophils and Neutrophil-Derived Elastase. Clinical and Developmental Immunology. 2012. Vol. 2012, no. 2012, pp.1-12.
https://search.emarefa.net/detail/BIM-493275
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-493275