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Open Access Green as soon as Postprint is submitted to ZB.
Collagen type V promotes the malignant phenotype of pancreatic ductal adenocarcinoma.
Cancer Lett. 356, 721-732 (2015)
Excessive matrix production by pancreatic stellate cells promotes local growth and metastasis of pancreatic ductal adenocarcinoma and provides a barrier for drug delivery. Collagen type V is a fibrillar, regulatory collagen up-regulated in the stroma of different malignant tumors. Here we show that collagen type V is expressed by pancreatic stellate cells in the stroma of pancreatic ductal adenocarcinoma and affects the malignant phenotype of various pancreatic cancer cell lines by promoting adhesion, migration and viability, also after treatment with chemotherapeutic drugs. Pharmacological and antibody-mediated inhibition of β1-integrin signaling abolishes collagen type V-induced effects on pancreatic cancer cells. Ablation of collagen type V secretion of pancreatic stellate cells by siRNA reduces invasion and proliferation of pancreatic cancer cells and tube formation of endothelial cells. Moreover, stable knock-down of collagen type V in pancreatic stellate cells reduces metastasis formation and angiogenesis in an orthotopic mouse model of ductal adenocarcinoma. In conclusion, paracrine loops involving cancer and stromal elements and mediated by collagen type V promote the malignant phenotype of pancreatic ductal adenocarcinoma and underline the relevance of epithelial-stromal interactions in the progression of this aggressive neoplasm.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Collagen Type V ; Epithelial-stromal Interaction ; Pancreatic Ductal Adenocarcinoma ; Pancreatic Stellate Cells ; β1-integrin; Ehlers-danlos-syndrome; Stellate Cells; Extracellular-matrix; Cancer Cells; Metastasis; Expression; Stroma; Carcinoma; Adhesion; Col5a1
Language
english
Publication Year
2015
Prepublished in Year
2014
HGF-reported in Year
2014
ISSN (print) / ISBN
0304-3835
e-ISSN
0304-3835
Journal
Cancer Letters
Quellenangaben
Volume: 356,
Issue: 2,
Pages: 721-732
Publisher
Elsevier
Publishing Place
Clare
Reviewing status
Peer reviewed
POF-Topic(s)
30205 - Bioengineering and Digital Health
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s)
Enabling and Novel Technologies
PSP Element(s)
G-500390-001
G-500300-001
G-500300-001
PubMed ID
25449434
WOS ID
WOS:000348005500045
Scopus ID
84919444408
Erfassungsdatum
2014-12-04