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

De Oliveira, Tiago and Abiatari, Ivane and Raulefs, Susanne and Sauliunaite, Danguole and Erkan, Mert and Kong, Bo and Friess, Helmut and Michalski, Christoph W and Kleeff, Jörg (2012) Syndecan-2 promotes perineural invasion and cooperates with K-ras to induce an invasive pancreatic cancer cell phenotype. Molecular cancer, 11. p. 19. ISSN 1476-4598

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Abstract

BACKGROUND We have identified syndecan-2 as a protein potentially involved in perineural invasion of pancreatic adenocarcinoma (PDAC) cells. METHODS Syndecan-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. RESULTS SDC-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. CONCLUSION SDC-2 is a novel (perineural) invasion-associated gene in PDAC which cooperates with K-ras to induce a more invasive phenotype.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Depositing User: Dr Ivane Abiatari
Date Deposited: 30 Apr 2015 05:25
Last Modified: 30 Apr 2015 05:25
URI: http://eprints.iliauni.edu.ge/id/eprint/2221

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