[Abstract]

 There were many possibilities for the aggressive progression of PDAC and the tumor microenvironment, but the major regulators of signaling pathways between many factors outside the tumor cells have not been elucidated. However, recently reported FAM20C suggested that regulating physiological functions by phosphorylation of secretory factors and the ecto-domain of cell membrane receptors. We found that the secretion of FAM20C was increased in cells derived from 30 patients with metastatic pancreatic cancer, which correlated with the secretion pattern of OPN compare with non-metastatic cells. The secretion of OPN decreased in kinase inactive cells as well as in FAM20C knock down cells, suggesting FAM20C is main regulator of OPN secretion. Moreover, FAM20C overexpressed cells induced metastases in liver-metastasized xenograft models. Additionally, FAM20C secretion was increased by TGFβ-1 and IL-4 in macrophages isolated from mouse bone marrow. Furthermore, the amount of F4/80+CD11b+CD206+MHCII+ TAM were increased and sustained during tumor growth in the FAM20C overexpressing xenograft model. We firstly suggested mechanism of metastasis that FAM20C accelerates tumor progression and metastasis by OPN secretion and TAM increase with tumor immune environment remodeling. Therefore, FAM20C has high value not only prognosis marker of progression but also as a therapeutic target.