Department of Surgery, Technische Universität München, Munich, Germany.
Mol Cancer. 2012 Apr 3;11:19. doi: 10.1186/1476-4598-11-19.
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.
我们已经鉴定出连接蛋白-2（syndecan-2）是一种可能参与胰腺导管腺癌（pancreatic ductal adenocarcinoma，PDAC）细胞神经周围浸润的蛋白。
分析了人正常胰腺、慢性胰腺炎和 PDAC 组织中的连接蛋白-2（syndecan-2，SDC-2）表达。进行了功能体外测定，以确定其在侵袭、迁移和信号转导中的作用。
SDC-2 在大多数检测的胰腺癌细胞系中表达，而在神经浸润性 PDAC 细胞克隆中上调。PDAC 组织样本中 SDC-2 有 2 种不同的表达模式：SDC-2 在癌细胞细胞质中的阳性表达和肿瘤周围的表达。尽管 SDC-2 沉默（使用特异性 siRNA 寡核苷酸）不影响锚定依赖性生长，但它显著降低了胰腺癌细胞系 T3M4 和 Su8686 的迁移和侵袭能力。在转录水平上，SDC-2 RNAi 后与迁移和侵袭相关的基因下调。此外，SDC-2 沉默降低了 K-ras 活性、Src 的磷酸化，以及进一步下游的 ERK2 磷酸化，而假定的 SDC-2 信号转导蛋白 p120GAP 的水平保持不变。
SDC-2 是 PDAC 中一种新的（神经周围）浸润相关基因，它与 K-ras 合作诱导更具侵袭性的表型。
