肿瘤相关巨噬细胞通过bFGF/PI3K-AKT轴激活Schwann细胞促进胰腺癌神经侵犯的机制研究

周围神经侵犯（PNI）是胰腺癌进展的重要方式，与胰腺癌不良预后相关，最近研究证明外周神经Schwann细胞迁移是胰腺癌PNI发生的先决条件。肿瘤相关巨噬细胞（TAMs）是免疫微环境中的主要细胞之一，其可促进胰腺癌的进展及PNI，但其能否激活Schwann细胞介导PNI，尚无相关研究。我们前期预实验：1）体外模拟神经侵犯模型证明胰腺癌TAMs能激活Schwann细胞并促其迁移；2）表达谱芯片及ELISA结果进一步提示TAMs主要通过分泌bFGF介导的Schwann细胞激活、迁移。据此，本项目首次提出假说“TAMs通过bFGF/PI3K-AKT轴激活Schwann细胞促进胰腺癌PNI”，拟通过小鼠胰腺癌神经转移模型、体外Schwann细胞迁移模型、基因测序等阐明其分子机制，为抑制胰腺癌进展寻找新的靶点，为后续研究“胰腺癌PNI+免疫微环境”靶向药物提供新的思路。

Perineural invasion (PNI) is an important way of progression in pancreatic cancer and is associated with poor prognosis. Recent studies demonstrated that Schwann cell migration is a prerequisite for the development of PNI in pancreatic cancer. Tumor-associated macrophages (TAMs) are one of the main cells in the immune microenvironment, which can promote the progression of pancreatic cancer and PNI, but whether it can activate Schwann cells to promote PNI has not been reported. Our preliminary experiments: 1) in vitro model proved that TAMs can activate Schwann cells and promote their migration in pancreatic cancer;2) gene expression profiles and ELISA assays further suggested that TAMs could activate Schwann cells and facilitate Schwann cell migration by secreting bFGF. On this basis, this study hypothesized that TAMs promote perineural invasion (PNI) in pancreatic cancer by Schwann cells activation via bFGF/PI3K-AKT axis. We are going to apply gene sequencing assay, Schwann cell migration assays in vitro and PNI model in vivo, to elucidate the molecular mechanism in activated Schwann cells. This study tends to supply a basis for new targets for inhibition of pancreatic cancer progression, providing a new perspective for follow-up studies to develop targeted drugs for pancreatic cancer PNI and immune microenvironment.