title: Syndecan-2 promotes perineural invasion and cooperates with K-ras to induce an invasive pancreatic cancer cell phenotype.
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.
  
  
  CONCLUSIONS
  SDC-2 is a novel (perineural) invasion-associated gene in PDAC which cooperates with K-ras to induce a more invasive phenotype.
authors.affiliation: Department of Surgery, Technische Universität München, Munich, Germany.
authors.forename: Tiago
authors.initials: T
authors.lastname: De Oliveira
authors.forename: Ivane
authors.initials: I
authors.lastname: Abiatari
authors.forename: Susanne
authors.initials: S
authors.lastname: Raulefs
authors.forename: Danguole
authors.initials: D
authors.lastname: Sauliunaite
authors.forename: Mert
authors.initials: M
authors.lastname: Erkan
authors.forename: Bo
authors.initials: B
authors.lastname: Kong
authors.forename: Helmut
authors.initials: H
authors.lastname: Friess
authors.forename: Christoph W
authors.initials: CW
authors.lastname: Michalski
authors.forename: Jörg
authors.initials: J
authors.lastname: Kleeff
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D050500:Pancreatitis, Chronic / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D053669:Syndecan-2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D053669:Syndecan-2