Hepatocyte growth factor/c-met signaling in regulating urokinase plasminogen activator in human stomach cancer: A potential therapeutic target for human stomach cancer.

The Korean Journal of Internal Medicine
Kyung Hee LeeJae-Ryong Kim

Abstract

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. We investigated the roles of HGF/c-Met in tumor progression and metastasis in NUGC-3 and MKN-28 stomach cancer cell lines. 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. 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.

References

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Aug 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·M P StoppelliR K Assoian
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Citations

Jun 19, 2012·Cancer Biotherapy & Radiopharmaceuticals·Ying-Yu Ma, Hou-Quan Tao
Jan 21, 2010·The Journal of Pharmacology and Experimental Therapeutics·B J YamamotoJ W Harding
May 6, 2011·Cancer Biology & Therapy·Daniel V T CatenacciRavi Salgia
Sep 30, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Shuang LiYi Ba

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Methods Mentioned

BETA
transfection
FCS
light microscopy
immunoprecipitation

Software Mentioned

Bio
- 1D

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