Skip to main content
Log in

Simultaneous up-regulation of urokinase-type plasminogen activator (uPA) and uPA receptor by hepatocyte growth factor/scatter factor in human glioma cells

  • Published:
Clinical & Experimental Metastasis Aims and scope Submit manuscript

Abstract

Several lines of evidence indicate that hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, c-Met, may play an important role in progression of human glioma. In this study, effects of HGF/SF on urokinase- type plasminogen activator (uPA)-mediated proteolysis network were examined in c-Met-positive human glioma cell lines. Treatment of the glioma cells with various concentrations of HGF/SF resulted in an enhanced secretion of uPA proteins accompanying increased transcription of uPA mRNA in a dose dependent fashion. The levels of uPA receptor (uPAR) mRNAs were also elevated simultaneously upon HGF/SF stimulation, and the cell-surface associated uPA activity was also elevated by the treatment. Since concomitant expression of HGF and its receptor c-Met are frequently observed in malignant gliomas, these results suggest that HGF/SF participates in invasive process of malignant glioma cells not only by its motility-stimulating activity but also through enhanced degradation of the extracellular matrix induced by autocrine activation of uPA proteolysis network.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Kwaan HC. The plasminogen-plasmin system in malignancy. Cancer Metastasis Rev 1992; 11: 291–311.

    Article  PubMed  CAS  Google Scholar 

  2. Andreasen PA, Kjøller L, Christensen L et al. The urokinase type plasminogen activator system in cancer metastasis: A review. Int J Cancer 1997; 72: 1–22.

    Article  PubMed  CAS  Google Scholar 

  3. Yamamoto M, Sawaya R, Mohanam S et al. Expression and localization of urokinase-type plasminogen activator in human astrocytomas in vivo. Cancer Res 1994; 54: 3656–61.

    PubMed  CAS  Google Scholar 

  4. Hsu DW, Efird JT, Hedley-Whyte ET. Prognostic role of urokinasetype plasminogen activator in human gliomas. Am J Pathol 1995; 147: 114–23.

    PubMed  CAS  Google Scholar 

  5. Ellis V, Pyke C, Eriksen J et al. The urokinase receptor: involvement in cell surface proteolysis and cancer invasion. Ann NY Acad Sci 1992; 667: 13–31.

    PubMed  CAS  Google Scholar 

  6. Yamamoto M, Sawaya R, Mohanam S et al. Expression and localization of urokinase-type plasminogen activator receptor in human gliomas. Cancer Res 1994; 54: 5016–20.

    PubMed  CAS  Google Scholar 

  7. Gladson CL, Pijuan-Thompson V, Olman MA et al. Up-regulation of urokinase and urokinase receptor genes in malignant astrocytoma. Am J Pathol 1995; 146: 1150–60.

    PubMed  CAS  Google Scholar 

  8. Boros P, Miller CM. Hepatocyte growth factor: A multifunctional cytokine. Lancet 1995; 345: 293–5.

    Article  PubMed  CAS  Google Scholar 

  9. Matsumoto K, Nakamura T. Emerging multipotent aspects of hepatocyte growth factor. J Biochem 1996; 591–600.

  10. Cooper CS, Park M, Blair DG et al. Molecular cloning of a new transforming gene from a chemically transformed human cell line. Nature 1984; 311: 29–33

    Article  PubMed  CAS  Google Scholar 

  11. Bottaro DP, Rubin JS, Faletto DL et al. Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product. Science 1991; 251: 802–4.

    PubMed  CAS  Google Scholar 

  12. Jiang W, Hiscox S, Matsumoto K, Nakamura T. Hepatocyte growth factor/scatter factor, its molecular, cellular and clinical implication in cancer. Crit Rev Oncol Hematol 1999; 29: 209–48.

    PubMed  CAS  Google Scholar 

  13. Moriyama T, Kataoka H, Koono M, Wakisaka S. Expression of hepatocyte growth factor/scatter factor and its receptor c-Met in brain tumors: Evidence for a role in progression of astrocytic tumors (Review). Int J Mol Med 1999; 3: 531–6.

    PubMed  CAS  Google Scholar 

  14. Moriyama T, Kataoka H, Tsubouchi H et al. Concomitant expression of hepatocyte growth factor (HGF), HGF activator and c-met genes in human glioma cells in vitro. FEBS Lett 1995; 372: 78–82.

    Article  PubMed  CAS  Google Scholar 

  15. Moriyama T, Kataoka H, Seguchi K et al. Effects of hepatocyte growth factor (HGF) on human glioma cells in vitro: HGF acts as a motility factor in glioma cells. Int J Cancer 1996; 66: 678–85.

    Article  PubMed  CAS  Google Scholar 

  16. Rosen EM, Laterra J, Joseph A et al. Scatter factor expression and regulation in human glial tumors. Int J Cancer 1996; 67: 248–55.

    Article  PubMed  CAS  Google Scholar 

  17. Koochekpour S, Jeffers M, Rulong S et al. Met and hepatocyte growth factor/scatter factor expression in human gliomas. Cancer Res 1997 57: 5391-8.

    PubMed  CAS  Google Scholar 

  18. Yamamoto S, Wakimoto H, Aoyagi M et al. Modulation of motility and proliferation of glioma cells by hepatocyte growth factor. Jpn J Cancer Res 1997; 88: 564–77.

    PubMed  CAS  Google Scholar 

  19. Lamszus K, Schmidt NO, Jin L et al. Scatter factor promotes motility of human glioma and neuromicrovascular endothelial cells. Int J Cancer 1998; 75: 19–28.

    Article  PubMed  CAS  Google Scholar 

  20. Hamasuna R, Kataoka H, Moriyama T et al. Regulation of matrix metalloproteinase-2 (MMP-2) by hepatocyte growth factor/scatter factor (HGF/SF) in human glioma cells: HGF/SF enhances MMP-2 expression and activation accompanying up-regulation of membrane type-1 MMP. Int J Cancer 1999; 82: 274–81.

    Article  PubMed  CAS  Google Scholar 

  21. Kataoka H, Uchino H, Asada Y et al. Analysis of tissue factor and tissue factor pathway inhibitor expression in human colorectal carcinoma cell lines and metastatic sublines to the liver. Int J Cancer 1997; 72: 878–84.

    Article  PubMed  CAS  Google Scholar 

  22. Sawaya R, Highsmith R. Plasminogen activator activity and molecular weight patterns in human brain tumors. J Neurosurg 1988; 68: 72–9.

    Google Scholar 

  23. Kinder OH, Berger MS, Mueller BA et al. Urokinase plasminogen activator is elevated in human astrocytic gliomas relative to normal adjacent brain. Oncol Res 1993; 5: 409–14.

    PubMed  CAS  Google Scholar 

  24. Mohanam S, Sawaya R, McCutcheon I et al. Modulation of in vitro invasion of human glioblastoma cells by urokinase-type plasminogen activator receptor antibody. Cancer Res 1993; 53: 4143–47.

    PubMed  CAS  Google Scholar 

  25. Mohanam S, Chintala SK, Go Y et al. In vitro inhibition of human glioblastoma cell line invasiveness by antisense uPA receptor. Oncogene 1997; 14: 1351–9.

    Article  PubMed  CAS  Google Scholar 

  26. Mohan PM, Chintala SK, Mohanam S et al. Adenovirus-mediated delivery of antisense gene to urokinase-type plasminogen activator receptor suppresses glioma invasion and tumor growth. Cancer Res 1999; 59: 3369–73.

    PubMed  CAS  Google Scholar 

  27. Go Y, Chintala SK, Mohanam S et al. Inhibition of in vitro tumorigenicity and invasiveness of a human glioblastoma cell line transfected with antisense uPAR vectors. Clin Exp Metastasis 1997; 15: 440–6.

    Article  PubMed  CAS  Google Scholar 

  28. Kitange G, Shibata S, Tokunaga Y et al. Ets-1 transcription factormediated urokinase-type plasminogen activator expression and invasion in glioma cells stimulated by serum and basic fibroblast growth factors. Lab Invest 1999; 79: 407–16.

    PubMed  CAS  Google Scholar 

  29. Jeffers M, Rong S, Vande Wounde GF et al. Enhanced tumorigenicity and invasion-metastasis by hepatocyte growth factor/scatter factormet signalling in human cells concomitant with induction of the urokinase proteolysis network. Mol Cell Biol 1996; 16: 1115–25.

    PubMed  CAS  Google Scholar 

  30. Paciucci R, Vila MA, Adell T et al. Activation of the urokinase plasminogen activator/urokinase plasminogen activator receptor system and redistribution of E-cadherin are associated with hepatocyte growth factor-induced motility of pancreas tumor cells overexpressing Met. Am J Pathol 1998; 153: 201–12.

    PubMed  CAS  Google Scholar 

  31. Li H, Shimura H, Aoki Y et al. Hepatocyte growth factor stimulates the invasion of gallbladder carcinoma cell lines in vitro. Clin Exp Metastasis 1998; 16: 74–82.

    Article  PubMed  CAS  Google Scholar 

  32. Rosen EM, Knesel J, Goldberg ID et al. Scatter factor modulates the metastatic phenotype of the EMT6 mouse mammary tumor. Int J Cancer 1994; 57: 706–14.

    PubMed  CAS  Google Scholar 

  33. Pepper MS, Matsumoto K, Nakamura T et al. Hepatocyte growth factor increases urokinase-type plasminogen activator (u-PA) and u-PA receptor expression in Madin-Darby canine kidney epithelial cells. J Biol Chem 1992; 267: 2049 3–6.

    Google Scholar 

  34. Laterra J, Nam M, Rosen EM et al. Scatter factor/hepatocyte growth factor gene transfer enhances glioma growth and angiogenesis in vivo. Lab Invest 1997; 76: 565–77.

    PubMed  CAS  Google Scholar 

  35. Abounader R, Ranganathan S, Lal B, et al. Reversion of human glioblastoma malignancy by U 1 small nuclear RNA/ribosome targeting of scatter factor/hepatocyte growth factor and c-met expression. J Natl Cancer Inst1999; 91: 1548–56

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Moriyama, T., Kataoka, H., Hamasuna, R. et al. Simultaneous up-regulation of urokinase-type plasminogen activator (uPA) and uPA receptor by hepatocyte growth factor/scatter factor in human glioma cells. Clin Exp Metastasis 17, 873–879 (1999). https://doi.org/10.1023/A:1006729611241

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1006729611241

Navigation