Collagen type V promotes the malignant phenotype of pancreatic ductal adenocarcinoma

被引：67

作者：

Berchtold, Sonja ^{[1
]}

Gruenwald, Barbara ^{[2
]}

Krueger, Achim ^{[2
]}

Reithmeier, Anja ^{[1
]}

Haehl, Teresa ^{[1
]}

Cheng, Tao ^{[3
]}

Feuchtinger, Annette ^{[4
]}

Born, Diana ^{[5
]}

Erkan, Mert ^{[3
,6
]}

Kleeff, Joerg ^{[3
]}

Esposito, Irene ^{[1
]}

机构：

[1] Tech Univ Munich, Inst Pathol, D-80290 Munich, Germany

[2] Tech Univ Munich, Inst Expt Oncol & Therapy Res, D-80290 Munich, Germany

[3] Tech Univ Munich, Dept Surg, D-80290 Munich, Germany

[4] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Analyt Pathol, Neuherberg, Germany

[5] Kantonspital Munsterlingen, Munsterlingen, Germany

[6] Koc Univ, Sch Med, Dept Surg, Istanbul, Turkey

来源：

CANCER LETTERS | 2015年 / 356卷 / 02期

基金：

欧盟第七框架计划;

关键词：

Collagen type V; beta; 1-integrin; Pancreatic ductal adenocarcinoma; Pancreatic stellate cells; Epithelial-stromal interaction; EHLERS-DANLOS-SYNDROME; STELLATE CELLS; EXTRACELLULAR-MATRIX; CANCER; EXPRESSION; STROMA; ADHESION; COL5A1; FIBRIL; IDENTIFICATION;

D O I：

10.1016/j.canlet.2014.10.020

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 beta 1-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 knockdown 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. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

引用

页码：721 / 732

页数：12