携带Tspan8、CD44v6的肿瘤干细胞外泌体对胰腺癌侵袭性的机制研究

肿瘤干细胞（CSC）是胰腺癌（PaCa）转移、复发的主要原因之一，同时外泌体（Exosomes）又在CSC与PaCa疾病进展中起着重要的“桥梁”作用。我们前期研究证实，CD44v6可作为PaCSC标志物，携带CD44v6的外泌体可增强肿瘤细胞的运动性及侵袭力，促进PaCa远处转移。此外，CD44v6基因缺失也会明显降低Tspan8的表达量，我们猜测也许Tspan8可以反向影响CD44v6表达，二者协同调节PaCSC生物特性，成为一个高效精准的CSC联动靶点，为PaCa精准靶向治疗找到重要突破口。既往尚未有关于CD44v6或Tspan8对外泌体黏附性及“运载物”调节、干扰的研究，而本课题将在确定CD44v6、Tspan8与PaCSC关系的基础上，进一步明确CD44v6、Tspan8对外泌体结构组分的影响，预测外泌体在调节PaCa进展中发挥作用的靶点miRNA。

Cancer stem cells (CSC), a small subpopulation of cancer cells with capability of self-renewal, high differentiation potential and drug resistance, which are one of the major causes of metastasis and recurrence in pancreatic cancer (PaCa). Exosomes play an important role in the crosstalk between CSC and PaCa. Previously, we demonstrated that CD44v6 acts as a CSC marker in PaCa which playing an important role in premetastatic niche formation via exosomes. CD44v6-competent exosomes enhance the tumor cells migration and invasion, and promote distant metastasis in PaCa. In addition, the expression of Tspan8 also was downregulated in CD44v6-knockdown cell lines significantly. Therefore, we suppose that Tspan8 maybe feedback and impact CD44v6 expression, both of Tspan8 and CD44v6 jointly regulate PaCSC biological characteristics. We considered it important to control whether CD44v6/Tspan8 play as CSC biomarker in human PaCa, and promote tumor metastasis, finally, propose new therapeutic strategies for targeted therapy. So far, no evidences suggest CD44v6 or Tspan8 impacts the adhesion and cargoes of exosomes. In this program, based on the association between CD44v6/Tspan8 and PaCSC, to demonstrate the impact of CD44v6 or Tspan8 on the components of exosomes, and to predict the target miRNAs which play a role in the progression of PaCa.