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KMID : 0338420060210010020
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The Korean Journal of Internal Medicine
2006 Volume.21 No. 1 p.20 ~ p.27
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Hepatocyte Growth Factor/c-Met Signaling in Regulating Urokinase Plasminogen Activator in Human Stomach Cancer: A Potential Therapeutic Target for Human Stomach Cancer
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Lee Kyung-Hee
Choi Eun-Young
Hyun Myung-Soo
Jang Byung-Ik
Kim Tae-Nyeun
Kim Sang-Woon
Song Sun-Kyo
Kim Jung-Hye
Kim Jae-Ryong
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Abstract
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Background: Up-regulation of the hepatocyte growth factor (HGF), its transmembrane tyrosine kinase receptor (c-Met), and urokinase type plasminogen activator (uPA), is associated with the development and metastasis of various types of cancers. However, the mechanisms by which HGF/c-Met signaling mediates cancer progression and metastasis are unclear.
Methods: We investigated the roles of HGF/c-Met in tumor progression and metastasis in NUGC-3 and MKN-28 stomach cancer cell lines.
Results: Treatment with HGF increased c-Met phosphorylation in a dose-dependent manner, as well as increasing cell proliferation. HGF treatment also increased the protein level and the activity of uPA in NUGC-3 and MKN-28 cells. A monoclonal antibody against human uPA receptor (uPAR), mAb 3936, inhibited HGF-mediated tumor cell invasion in a dose-dependent manner. Down-regulation of uPA using uPA-shRNA induced a decrease in in vitro cell invasion in NUGC-3 cells.
Conclusions: These results suggest that NUGC-3 and MKN-28 cells express functional c-Met, which may provide a therapeutic target for interfering with metastases of cancer cells by inhibiting uPA and uPAR-mediated proteolysis.
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KEYWORD
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Metastasis, uPA, uPAR inhibition, Invasion
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