Cancer Research and Treatment

Original Article

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 Res Treat. 2003;35(3):207-212. Published online June 30, 2003; DOI: https://doi.org/10.4143/crt.2003.35.3.207

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.

Citations

Citations to this article as recorded by

PP2A complex disruptor SET prompts widespread hypertranscription of growth-essential genes in the pancreatic cancer cells
He Xu, Di Wu, Mingming Xiao, Yubin Lei, Yalan Lei, Xianjun Yu, Si Shi
Science Advances.2024;[Epub] CrossRef
Reactive oxygen species regulate the generation of urokinase plasminogen activator in human hepatoma cells via MAPK pathways after treatment with hepatocyte growth factor
Kyung Hee Lee, Jae-Ryong Kim
Experimental and Molecular Medicine.2009; 41(3): 180. CrossRef
Reactive oxygen species regulate urokinase plasminogen activator expression and cell invasion via mitogen-activated protein kinase pathways after treatment with hepatocyte growth factor in stomach cancer cells
Kyung Hee Lee, Sang Woon Kim, Jae-Ryong Kim
Journal of Experimental & Clinical Cancer Research.2009;[Epub] CrossRef
Cellular Mechanisms of Hepatocyte Growth Factor-Mediated Urokinase Plasminogen Activator Secretion by MAPK Signaling in Hepatocellular Carcinoma
Kyung Hee Lee, Eun Young Choi, Myung Soo Hyun, Jong Ryul Eun, Byung Ik Jang, Tae Nyeun Kim, Heon Ju Lee, Dong Shik Lee, Sung Su Yun, Hong Jīn Kim, Jung Hye Kim, Jae-Ryong Kim
Tumori Journal.2008; 94(4): 523. CrossRef
Association of Extracellular Cleavage of E-Cadherin Mediated by MMP-7 with HGF-Induced in vitro Invasion in Human Stomach Cancer Cells
K.H. Lee, E.Y. Choi, M.S. Hyun, B.I. Jang, T.N. Kim, S.W. Kim, S.K. Song, J.H. Kim, J.-R. Kim
European Surgical Research.2007; 39(4): 208. CrossRef
Hepatocyte Growth Factor/c-Met Signaling in Regulating Urokinase Plasminogen Activator in Human Stomach Cancer: A Potential Therapeutic Target for Human Stomach Cancer
Kyung Hee Lee, Eun Young Choi, Myung Soo Hyun, Byung Ik Jang, Tae Nyeun Kim, Sang Woon Kim, Sun Kyo Song, Jung Hye Kim, Jae-Ryong Kim
The Korean Journal of Internal Medicine.2006; 21(1): 20. CrossRef
Expression of E-Cadherin and uPA and their Association with the Prognosis of Pancreatic Cancer
Sang Joon Shin, Kyeong Ok Kim, Min Kyoung Kim, Kyung Hee Lee, Myung Soo Hyun, Keuk Jun Kim, Joon Hyuk Choi, Hong Seok Song
Japanese Journal of Clinical Oncology.2005; 35(6): 342. CrossRef

3,683 View
21 Download
7 Crossref

First
Prev
Page of 1
Next
Last

Search