摘要
胰腺癌（PC）的诊断频率排名第12位，但它是癌症相关死亡的第四大主要原因，其5年生存率不到7％。由于PC的早期阶段通常没有症状，因此预后较差。几种生长因子，尤其是血管内皮生长因子（VEGF）的过度表达与PC有关，导致信号转导通路功能异常并促进肿瘤生长，侵袭和转移。肝细胞生长因子（HGF）通过Met受体发挥作用，并且由于开发阻止Met受体及其信号转导途径的治疗方法而不断受到研究关注。巨噬细胞刺激蛋白（MSP）及其受体Ron在PC的病因学中也被认为是重要的，但研究较少。尽管血管紧张素II（AngII）/ AT1受体系统以介导血压和体内水/电解质平衡而闻名，但它还可以通过刺激VEGF的表达促进肿瘤血管形成和生长。血管紧张素IV（AngIV）是AngII的代谢产物，与HGF和MSP的“铰链区”具有序列同源性，这是Met和Ron受体激活所必需的生长因子二聚化过程中的关键结构。我们已经开发了基于AngIV的类似物，旨在阻止HGF和MSP的二聚化，从而阻止受体激活。通过使用PC细胞培养物，Norleual已显示出希望。结果表明，在该原位PC小鼠模型中，该类似物抑制了细胞迁移，侵袭和促存活功能，并且显着抑制了肿瘤的生长。
关键词: 胰腺癌，血管紧张素IV，肝细胞生长因子，met受体，巨噬细胞刺激蛋白，Ron受体。
图形摘要
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