Role of hepatocyte growth factor/c-Met signaling in regulating urokinase plasminogen activator on invasiveness in human hepatocellular carcinoma: a potential therapeutic target

  • Kyung Hee Lee
  • Eun Young Choi
  • Myung Soo Hyun
  • Byung Ik Jang
  • Tae Nyeun Kim
  • Heon Ju Lee
  • Jong Yuel Eun
  • Hong Gin Kim
  • Sung Soo Yoon
  • Dong Sik Lee
  • Jung Hye Kim
  • Jae-Ryong Kim
Research Paper

DOI: 10.1007/s10585-007-9106-6

Cite this article as:
Lee, K.H., Choi, E.Y., Hyun, M.S. et al. Clin Exp Metastasis (2008) 25: 89. doi:10.1007/s10585-007-9106-6

Abstract

Hepatocyte growth factor (HGF), its transmembrane tyrosine kinase receptor (c-Met), and urokinase type plasminogen activator (uPA) is a key protein in the plasminogen activation system, which plays a proteolytically important role in the invasion and metastasis of various types of cancers. However, the mechanisms by which HGF/c-Met signaling mediates cancer progression and metastasis are unclear. This study was designed to investigate the roles of HGF/c-Met in tumor progression and metastasis in HepG2 and Hep3B hepatoma cell lines. Treatment with HGF increased c-Met phosphorylation in a dose-dependent manner. Activity of c-Met phosphorylation peaked 1–3 min after HGF treatment and then declined. HGF enhanced the protein level and the activity of uPA in HepG2 and Hep3B cells, and the uPAR protein level also increased in a HGF dose-dependent manner. HGF increased cell invasion through the Matrigel. A monoclonal antibody against human uPA receptor, 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. These results suggest that hepatoma cells express functional c-Met, which may provide a target for a therapeutic basis to interfere with metastases of cancer cells by inhibiting uPA system-mediated proteolysis.

Keywords

Metastasis uPA uPAR inhibition ERK 

Copyright information

© Springer Science+Business Media B.V. 2007

Authors and Affiliations

  • Kyung Hee Lee
    • 1
  • Eun Young Choi
    • 1
  • Myung Soo Hyun
    • 1
  • Byung Ik Jang
    • 2
  • Tae Nyeun Kim
    • 2
  • Heon Ju Lee
    • 2
  • Jong Yuel Eun
    • 2
  • Hong Gin Kim
    • 3
  • Sung Soo Yoon
    • 3
  • Dong Sik Lee
    • 3
  • Jung Hye Kim
    • 4
  • Jae-Ryong Kim
    • 4
    • 5
  1. 1.Department of Hemato-Oncology, College of MedicineYeungnam UniversityDaeguRepublic of Korea
  2. 2.Department of Gastro-Enterology, College of MedicineYeungnam UniversityDaeguRepublic of Korea
  3. 3.Department of General Surgery, College of MedicineYeungnam UniversityDaeguRepublic of Korea
  4. 4.Department of Biochemistry and Molecular Biology, College of medicineYeungnam UniversityDaeguRepublic of Korea
  5. 5.Aging-associated Vascular Disease Research Center, College of MedicineYeungnam UniversityDaeguRepublic of Korea

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