ST2蛋白抑制胃癌腹膜转移机制的研究

ST2 protein is a molecule which we have screened from peritoneal metastasis of gastric cancer cells and plays a critical role in inflammatory diseases and cardiovascular diseases. Recent studies have shown that ST-2 protein has some relations in tumorigenesis and tumor development, but it is still not known in peritoneal metastasis of gastric cancer. Using a phage display library, we obtained a peptide named PIII which can specifically bind cell surface in high peritoneal metastasis of gastric cancer cells. Furthermore, screened differentially expressed genes, and combined with affinity chromatography technology, we obtained peptide PⅢ receptor ST2 protein. Our preliminary study provides evidence that ST-2 protein is high expression in peritoneal metastasis of gastric cancer cells. we plan to use recombinant technology, protein technology and animal experiments to explore the relationship between ST2 protein and peritoneal metastasis in vitro and in vivo. Screening for ST2 protein's downstream or upstream effect molecules by means of high-throughput, we further explore the ST2 signal transduction mechanism by antibodies or blocking agent intervention in peritoneal metastasis of gastric cancer. It will be revealed the biological mechanism of ST2 in peritoneal metastasis of gastric cancer.

ST2蛋白是我们筛选出的与胃癌腹膜转移密切相关的分子，在炎症性疾病、心血管疾病中起着重要作用,近来的研究表明ST2蛋白和肿瘤发生发展之间具有某种联系，与胃癌腹膜转移的研究仍为空白。我们通过噬菌体随机肽库筛选技术筛选出与胃癌腹膜高转移细胞表面受体特异性结合的多肽PⅢ, 进一步通过筛选差异表达基因，结合亲和层析技术，获得多肽PⅢ的受体分子ST2蛋白，初步研究显示ST2在胃癌腹膜转移细胞中表达增高。本项目进一步研究ST2在胃癌腹膜转移中的作用，利用基因重组、蛋白质技术、动物试验等体内外方法探讨ST2与胃癌腹膜转移的关系，通过高通量的方法筛选ST2在胃癌腹膜转移中发挥功能的上下游效应分子，进一步探索其信号转导机制，通过抗体或阻断剂等干预手段研究ST2及其效应分子影响胃癌腹膜转移的作用，有助于揭示ST2对胃癌腹膜转移的的生物学功能机制

腹膜转移是胃癌死亡的主要原因之一，已发现的转移相关分子不能完全解释其机制。ST2蛋白在炎症性疾病、心血管疾病中起着重要作用，近来的研究表明ST2蛋白和肿瘤发生发展之间具有某种联系，然而与胃癌腹膜转移的研究仍为空白。我们通过噬菌体随机肽库筛选技术筛选出与胃癌腹膜高转移细胞表面受体特异性结合的多肽PⅢ，进一步通过筛选差异表达基因，结合亲和层析技术，获得多肽PⅢ的受体分子ST2蛋白。课题组按计划应用Western Blot和免疫组化方法证实ST2在胃癌转移组织中表达状态分析其临床意义。研究证实ST2表达水平在胃癌临床标本中较癌旁正常组织普遍。结合临床病理资料统计分析，ST2蛋白表达下调与胃癌病理分期、临床TNM分期和淋巴结转移显著相关。课题组继续通过高通量的方法筛选ST2在胃癌腹膜转移中发挥功能的上下游效应分子，进一步探索其信号转导机制。通过高通量的方法筛选出和ST2蛋白相互作用的microRNA并选取数个（miR-214、miR-29b、miR-181a-5p和miR-29a-3p）进行生物学功能验证。上述工作的开展，培养硕士研究生共4人，发表SCI文章1篇，中文期刊文章3篇（包括中文核心期刊2篇）。另有一篇文章目前已被SCI收录期刊Molecular Medicine Reports正式接收待发表。