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
;
: 20-27, 2006.
Article
in English
| WPRIM
| ID: wpr-17044
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Stomach Neoplasms
/
Urokinase-Type Plasminogen Activator
/
Adenocarcinoma
/
Signal Transduction
/
Hepatocyte Growth Factor
/
Receptors, Growth Factor
/
Receptor Protein-Tyrosine Kinases
/
Disease Progression
/
Proto-Oncogene Proteins c-met
/
Neoplasm Metastasis
Limits:
Humans
Language:
English
Journal:
The Korean Journal of Internal Medicine
Year:
2006
Type:
Article
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