Hepatocyte Growth Factor/c-Met Signaling in Regulating Urokinase Plasminogen Activator in Human Stomach Cancer: A Potential Therapeutic Target for Human Stomach Cancer.
10.3904/kjim.2006.21.1.20
- Author:
Kyung Hee LEE
1
;
Eun Young CHOI
;
Myung Soo HYUN
;
Byung Ik JANG
;
Tae Nyeun KIM
;
Sang Woon KIM
;
Sun Kyo SONG
;
Jung Hye KIM
;
Jae Ryong KIM
Author Information
1. Department of Hemato-oncology, Yeungnam University College of Medicine, Daegu, Korea.
- Publication Type:Original Article ; In Vitro ; Research Support, Non-U.S. Gov't
- Keywords:
Metastasis;
uPA;
uPAR inhibition;
Invasion
- MeSH:
Urinary Plasminogen Activator/antagonists & inhibitors/*metabolism;
Stomach Neoplasms/drug therapy/*enzymology;
Signal Transduction/*drug effects;
Receptors, Growth Factor/*drug effects;
Receptor Protein-Tyrosine Kinases/*drug effects;
Proto-Oncogene Proteins c-met/*drug effects;
Neoplasm Metastasis;
Humans;
Hepatocyte Growth Factor/*metabolism;
Disease Progression;
Adenocarcinoma/drug therapy/enzymology
- From:The Korean Journal of Internal Medicine
2006;21(1):20-27
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.
