논문검색
Author Kyung Hee Lee, M.D., Myung Soo Hyun, M.D. and Jae-Ryong Kim, M.D., Ph.D.1
Place of duty Departments of Hemato-Oncology and 1Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, Daegu, Korea
Title Invasion-Metastasis by Hepatocyte Growth Factor/c-Met Signaling Concomitant with Induction of Urokinase Plasminogen Activator in Human Pancreatic Cancer:
Publicationinfo Cancer Research and Treatment 2003 Jun; 035(03): 207-212.
Key_word Metastasis, uPA, uPAR inhibition, ERK
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Abstract Purpose: Increased expression of the hepatocytes growth factor (HGF) receptor (c-Met) and urokinase type plasminogen activator (uPA) correlate with the development and metastasis of cancers. However, the mechanisms by which HGF/c-Met signaling mediate cancer progression and metastasis are unclear. Therefore, we investigated the roles of HGF/c-Met in tumor progression and metastasis in pancreatic cancer cell lines, L3.6PL and IMIN-PC2. Materials and Methods: To see the functional c-Met protein, we were performed immunoprecipitation for functional c-Met protein. And also performed western bolot analysis and gel zymography for the functional uPA protein. To see the inhibition effects of uPAR monoclonal antibody on invasiveness of two pancreatic cancer cell lines, we were carried out standard two chamber invasion assay. Results: At first, we observed the HGF-mediated c-Met phosphorylation and cell growth. c-Met phosphorylation was increased in the HGF-treated cells in a dose depen- dent manner. HGF resulted in increments of cell growth and ERK phosphorylation. HGF treatment increased the uPA expression and the uPA activity. A monoclonal antibody 3936, specific to uPAR receptor, inhibited HGF- mediated tumor cell invasion in a dose dependent manner. Conclusion: These results suggest that functional c- Met and HGF/c-Met signaling up-regulate the activity of uPA and result in increments of invasion-metastasis in the pancreatic cancer cells. (Cancer Research and Treatment 2003;35:207 212)