Collagen type V promotes the malignant phenotype of pancreatic ductal adenocarcinoma. Issue 2 (28th January 2015)

• Record Type: Journal Article
• Authors: Berchtold, Sonja; Grünwald, Barbara; Krüger, Achim; Reithmeier, Anja; Hähl, Teresa; Cheng, Tao; Feuchtinger, Annette; Born, Diana; Erkan, Mert; Kleeff, Jörg; Esposito, Irene
• Is Part Of: Cancer letters. Volume 356:Issue 2(2015)Part B
• Page Start: 721
• Page End: 732
• Publication Date: 2015-01-28
• Subjects: PSC pancreatic stellate cells -- PDAC pancreatic ductal adenocarcinoma -- Col V collagen type V -- αSMA α-smooth muscle actin; Collagen type V -- β1-integrin -- Pancreatic ductal adenocarcinoma -- Pancreatic stellate cells -- Epithelial–stromal interaction; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2014.10.020
• Languages: English
• ISSNs: 0304-3835

Abstract

Highlights: Col V is aberrantly overexpressed during progression of PDAC and often co-localized with its receptor β1-integrin. Col V affects viability, adhesion, migration, and metastatic potential of pancreatic cancer cells. The β1-integrin/FAK signaling pathway is identified as important mediator of Col V effects on tumor cells· Col V and its downstream pathway represent possible therapeutic targets in PDAC. Abstract: 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.