Plasminogen activator inhibitor-1 (PAI-1) gene transfection inhibits the liver metastasis of pancreatic cancer by preventing angiogenesis

Abstract

Plasminogen activator inhibitor-1 (PAI-1) is a unique type of serine protease inhibitor and one of the key regulators of tumor invasion and metastasis. The purpose of this study was to elucidate the effect of PAI-1 gene transfection on liver metastasis and its mechanism by using the human high liver metastasis pancreatic cancer cell line, SW1990. PAI-1-transfected SW1990 (SW/PAI-1) produced a significantly higher level of PAI-1 in supernatant than parental cells. While no difference was observed for the production of u-PA and u-PA activity in the supernatant, cell proliferation of SW/PAI-1 was slightly suppressed on the 7th day of incubation compared to parental cells. Cellular invasion, in vivo tumorigenesis in xenograft and liver metastasis were significantly suppressed in SW/PAI-1 cells compared to parental cells. The angiogenesis of xenograft by detecting microvascular density and the production of metastasis-related factors, such as VEGF and TGF-beta1, were also decreased in SW/PAI-1 cells. These findings suggested that PAI-1 gene transfection might have the ability to prevent the liver metastasis of pancreatic cancer by modulating angiogenesis.