Extracellular S100A11 secreted by PDAC activates surrounding fibroblasts through the S100A11-RAGE-tumor progression locus 2 (TPL2)-cyclooxygenase 2 (COX2) pathway, which can induce the production of prostaglandin E2 (PGE2), a key soluble factor that accelerates PDAC cell motility and ultimately leads to an increase in the number of PDAC-derived circulating tumor cells (CTCs) (79). This evidence concerns the gene MAP3K8 and neoplasm.