Invasion-Metastasis by Hepatocyte Growth Factor/c-Met Signaling Concomitant with Induction of Urokinase Plasminogen Activator in Human Pancreatic Cancer: Role as Therapeutic Target

Kyung Hee Lee; Myung Soo Hyun; Jae Ryong Kim

doi:10.4143/crt.2003.35.3.207

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Invasion-Metastasis by Hepatocyte Growth Factor/c-Met Signaling Concomitant with Induction of Urokinase Plasminogen Activator in Human Pancreatic Cancer: Role as Therapeutic Target: Kyung Hee Lee, Myung Soo Hyun, Jae Ryong Kim; Cancer Research and Treatment 2003;35(3): 207-212.
DOI: https://doi.org/10.4143/crt.2003.35.3.207
Published online: June 30, 2003

¹Department of Hemato-Oncology, Yeungnam University, Daegu,Korea. lkhee@med.yu.ac.kr
²Department of Biochemistry and Molecular Biology, College ofMedicine, Yeungnam University, Daegu, Korea.

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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 dependent 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.

Keywords: Metastasis;uPA;uPAR inhibition;ERK

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Invasion-Metastasis by Hepatocyte Growth Factor/c-Met Signaling Concomitant with Induction of Urokinase Plasminogen Activator in Human Pancreatic Cancer: Role as Therapeutic Target

Cancer Res Treat. 2003;35(3):207-212. Published online June 30, 2003

DOI: https://doi.org/10.4143/crt.2003.35.3.207