Cancer associated fibroblasts (CAFs) derived exosomes with A promoted liver metastasis of pancreatic cancer by regulating C through transcription factor B

Abstract Cancer-associated fibroblasts (CAFs) comprise the majority of the tumor bulk of pancreatic ductal adenocarcinomas (PDACs). Despite the long-standing recognition of the prominence of CAFs in PDAC, the effect of extracellular vesicles derived from CAFs on the liver metastasis of PDACs cells is not well characterized. The aim of this study was to determine whether specific derived from CAFs might be involved in liver metastasis in PDACs. We found that CAFs are intrinsically related with liver metastasis and thus the potential role of CAFs in PDACs was highlighted. Further, CAFs significantly increase the release of extracellular vesicles wit A and it caused increased liver metastasis. Advanced experiments demonstrated that, C, in recipient epithelial cells and promote proliferation, was up-regulated by A in EVs from CAFs. Besides, treatment of an inhibitor of A as well as an inhibitor of exosome release, GW4869, significantly reduces the activation of B, thus decreased the activity of C. Collectively, these findings show the potential for exosome inhibitors as treatment options for overcoming PDAC liver metastasis.