The online version of this article (doi:10.1186/1476-4598-11-19) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
TDO, IA, SR and DS carried out the experiments; TDO, IA, SR, DS, ME, BK and CWM analyzed data. TDO, CWM, IA, HF and JK drafted the manuscript. CWM, TDO, ME, BK, HF and JK designed the study. HF, JK and CWM coordinated the study. All authors read and approved the final draft of the manuscript. TDO and IA contributed equally to the study.
We have identified syndecan-2 as a protein potentially involved in perineural invasion of pancreatic adenocarcinoma (PDAC) cells.
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.
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.
SDC-2 is a novel (perineural) invasion-associated gene in PDAC which cooperates with K-ras to induce a more invasive phenotype.
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- Syndecan-2 promotes perineural invasion and cooperates with K-ras to induce an invasive pancreatic cancer cell phenotype
Tiago De Oliveira
Christoph W Michalski
- BioMed Central
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