Syndecan-2 promotes perineural invasion and cooperates with K-ras to induce an invasive pancreatic cancer cell phenotype

Molecular Cancer

Research

Susanne Raulefs¹  Bo Kong¹  Mert Erkan¹  Ivane Abiatari¹  Danguole Sauliunaite¹  Jörg Kleeff¹  Helmut Friess¹  Christoph W Michalski¹  Tiago De Oliveira² 

[1] Department of Surgery, Technische Universität München, Munich, Germany;Department of Surgery, Technische Universität München, Munich, Germany;International Max Planck Research School, Martinsried-Munich, Germany;

关键词: Pancreatic Cancer;    Pancreatic Cancer Cell;    Perineural Invasion;    Pancreatic Cancer Cell Line;    Normal Pancreas;   

DOI  :  10.1186/1476-4598-11-19

 received in 2010-12-15, accepted in 2012-04-03,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundWe have identified syndecan-2 as a protein potentially involved in perineural invasion of pancreatic adenocarcinoma (PDAC) cells.MethodsSyndecan-2 (SDC-2) expression was analyzed in human normal pancreas, chronic pancreatitis and PDAC tissues. Functional in vitro assays were carried out to determine its role in invasion, migration and signaling.ResultsSDC-2 was expressed in the majority of the tested pancreatic cancer cell lines while it was upregulated in nerve-invasive PDAC cell clones. There were 2 distinct expression patterns of SDC-2 in PDAC tissue samples: SDC-2 positivity in the cancer cell cytoplasm and a peritumoral expression. Though SDC-2 silencing (using specific siRNA oligonucleotides) did not affect anchorage-dependent growth, it significantly reduced cell motility and invasiveness in the pancreatic cancer cell lines T3M4 and Su8686. On the transcriptional level, migration-and invasion-associated genes were down-regulated following SDC-2 RNAi. Furthermore, SDC-2 silencing reduced K-ras activity, phosphorylation of Src and - further downstream - phosphorylation of ERK2 while levels of the putative SDC-2 signal transducer p120GAP remained unaltered.ConclusionSDC-2 is a novel (perineural) invasion-associated gene in PDAC which cooperates with K-ras to induce a more invasive phenotype.

【 授权许可】

Unknown   
© De Oliveira et al; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.