title: Collagen type V promotes the malignant phenotype of pancreatic ductal adenocarcinoma.
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.
authors.affiliation: Institute of Pathology, Technische Universität München, Munich, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Berchtold
authors.affiliation: Institute for Experimental Oncology and Therapy Research, Technische Universität München, Munich, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Grünwald
authors.affiliation: Institute for Experimental Oncology and Therapy Research, Technische Universität München, Munich, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Krüger
authors.affiliation: Institute of Pathology, Technische Universität München, Munich, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Reithmeier
authors.affiliation: Institute of Pathology, Technische Universität München, Munich, Germany.
authors.forename: Teresa
authors.initials: T
authors.lastname: Hähl
authors.affiliation: Department of Surgery, Technische Universität München, Munich, Germany.
authors.forename: Tao
authors.initials: T
authors.lastname: Cheng
authors.affiliation: Research Unit Analytical Pathology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Feuchtinger
authors.affiliation: Pathology, Kantonspital Münsterlingen, Münsterlingen, Switzerland.
authors.forename: Diana
authors.initials: D
authors.lastname: Born
authors.affiliation: Department of Surgery, Technische Universität München, Munich, Germany; Department of Surgery, Koc University School of Medicine, Istanbul, Turkey.
authors.forename: Mert
authors.initials: M
authors.lastname: Erkan
authors.affiliation: Department of Surgery, Technische Universität München, Munich, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Kleeff
authors.affiliation: Institute of Pathology, Technische Universität München, Munich, Germany. Electronic address: esposito@lrz.tum.de.
authors.forename: Irene
authors.initials: I
authors.lastname: Esposito
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D024062:Collagen Type V / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010179:Pancreas / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D058954:Pancreatic Stellate Cells / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D023041:Xenograft Model Antitumor Assays
chemical_list: D024062:Collagen Type V; D019012:Integrin beta1; D012333:RNA, Messenger; D034741:RNA, Small Interfering
keywords: Collagen type V; Epithelial–stromal interaction; Pancreatic ductal adenocarcinoma; Pancreatic stellate cells; β1-integrin