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.
MeSH terms
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Animals
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Cell Line, Tumor
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Cell Movement
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Cell Proliferation
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Culture Media, Conditioned / chemistry
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Enzyme-Linked Immunosorbent Assay
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Humans
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Immunohistochemistry
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Liver Neoplasms / prevention & control
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Liver Neoplasms / secondary*
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Neovascularization, Pathologic / metabolism
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Neovascularization, Pathologic / pathology*
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Neovascularization, Pathologic / prevention & control
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Pancreatic Neoplasms / blood supply
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Pancreatic Neoplasms / genetics
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Pancreatic Neoplasms / pathology*
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Plasminogen Activator Inhibitor 1 / analysis
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Plasminogen Activator Inhibitor 1 / genetics
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Plasminogen Activator Inhibitor 1 / physiology*
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Platelet Endothelial Cell Adhesion Molecule-1 / analysis
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Transfection
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Transforming Growth Factor beta / analysis
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Transforming Growth Factor beta1
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Urokinase-Type Plasminogen Activator / analysis
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Vascular Endothelial Growth Factor A / analysis
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Xenograft Model Antitumor Assays / methods
Substances
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Culture Media, Conditioned
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Plasminogen Activator Inhibitor 1
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Platelet Endothelial Cell Adhesion Molecule-1
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TGFB1 protein, human
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Tgfb1 protein, mouse
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Transforming Growth Factor beta
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Transforming Growth Factor beta1
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Vascular Endothelial Growth Factor A
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Urokinase-Type Plasminogen Activator