胰腺癌易发生肝转移，与肝脏基质微环境富含星状细胞相关。我们通过胰腺癌原发灶和肝转移灶转录组测序和生物信息学分析，发现胰岛素样生长因子结合蛋白2（IGFBP2）很可能是沟通胰腺癌-肝脏基质关键分子。进一步实验显示胰腺癌细胞IGFBP2表达受OBSL1(Obscurin like 1)调控，IGFBP2可上调肝星状细胞VEGF表达，重塑肝转移微血管，促进胰腺癌生长与肝转移灶形成。本课题拟进一步研究胰腺癌OBSL1/IGFBP2上调肝星状细胞VEGF表达的具体机制、IGFBP2/VEGF在肝脏转移微环境中的作用，阐明胰腺癌肝转移关键通路。建立模拟胰腺细胞恶变进程的转基因小鼠模型，利用我们已建立的纳米技术平台实现体内示踪胰腺癌肝转移，通过联合负载抗IGFBP2和VEGF单链抗体纳米微粒切断胰腺癌-肝星状细胞联系，为寻找胰腺癌肝转移治疗新靶点提供新思路。

Liver metastasis usually occurs in pancreatic cancer, which is related to the richness of hepatic stellate cells in the microenvironment of liver matrix，and liver metastases are rich in matrix tissue. We found that insulin-like growth factor binding protein 2 (IGFBP2) is likely to be key molecular in communication of pancreatic cancer and liver matrix by the transcriptome sequencing and bioinformatics analysis of the primary focal pancreatic cancer and liver metastases. Further experiments showed that the expression of IGFBP2 in pancreatic cancer cells was regulated by OBSL1 (Obscurin like 1), and IGFBP2 could increase VEGF expression of hepatic stellate cells to remodel microvasculars of liver metastases to promote pancreatic cancer growth and the formation of liver metastasis. This research intends to further explore the specific effect of OBSL1/IGFBP2 on increasing VEGF expression and the liver matrix microenvironment related with liver metastasis, so that we can elucidate the critical pathway of liver metastasis of pancreatic cancer. We established simulation of transgenic mouse models of pancreatic cell malignant transformation and tumor metastasis, and used our nano technology platform to realize the body tracer of liver metastasis in pancreatic cancer. By using nanoparticles conjugating the single chain antibodies of IGFBP2 and VEGF to cut off the pancreatic cancer - hepatic stellate cell contact, we explore the new strategy in the treatment for liver metastasis in pancreatic cancer.