Fig. 3

Mechanism of targeted metastasis of pancreatic cancer to liver and lung. Upon arrival in the liver, sEVs derived from pancreatic cancer first express the integrin αVβ5 they carry, which promotes the release of pro-inflammatory factor S100A8 by activating Kupffer cells, making the liver an inflammatory environment. The CD44v6/C1QBP complex carried by sEVs also has the same mechanism by phosphorylating insulin-like growth factor 1 signaling molecules, thereby initiating the development of liver fibrosis. Secondly, the sEVs secreted by fibroblasts promote the expression of serum amyloid protein and STAT3 by releasing the pro-inflammatory factor IL-6 and binding to the IL-6 receptor on the liver, and the liver becomes an inflammatory and immunosuppressive environment by recruiting immunosuppressive cells. SEVs ITGα6β4 and ITGα6β1 bind to lung cells and epithelial cells and regulate lung specific metastasis by forming an inflammatory environment in the lung