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.

• Authors: Masafumi Inoue, Tetsuji Sawada, Yasutake Uchima, Kenjiro Kimura, Tamahiro Nishihara, Hiroaki Tanaka, Masakazu Yashiro, Nobuya Yamada, Masaichi Ohira, Kosei Hirakawa
• Journal: Oncology reports (Oncol Rep) Vol. 14 Issue 6 Pg. 1445-51 (Dec 2005) ISSN: 1021-335X [Print] Greece
• PMID: 16273237 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Culture Media, Conditioned
• Plasminogen Activator Inhibitor 1
• Platelet Endothelial Cell Adhesion Molecule-1
• TGFB1 protein, human
• Tgfb1 protein, mouse
• Transforming Growth Factor beta
• Transforming Growth Factor beta1
• Vascular Endothelial Growth Factor A
• Urokinase-Type Plasminogen Activator

Topics

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