The potential lymphangiogenic effects of hepatocyte growth factor/scatter factor in vitro and in vivo

  • Authors:
    • Wen G. Jiang
    • Gaynor Davies
    • Tracey A. Martin
    • Christian Parr
    • Gareth Watkins
    • Robert E. Mansel
    • Malcolm D. Mason
  • View Affiliations

  • Published online on: October 1, 2005     https://doi.org/10.3892/ijmm.16.4.723
  • Pages: 723-728
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Lymphangiogenesis is key to the lymphatic spread of cancer cells. The current study examined the potential effect of hepatocyte growth factor (HGF), a factor known to have strong biological effects on endothelial cells, on the lymphangiogenic function of endothelial cells and the formation of lymphatic vessels using both in vitro and in vivo models. Human endothelial cells that have lymphatic characteristics, human prostate and breast cancer cells PC-3 and MDA MB 231, were used. Expression of lymphatic markers, podoplanin, Prox-1, vascular endothelial growth factor receptor 3 (VEGF-R3) and LYVE-1 was determined using reverse transcription polymerase reaction and quantitative PCR. In nude mice prostate and breast xenograft tumour models, either HGF or an HGF-producing fibroblast cell line MRC-5 was given with or without the HGF antagonist, NK4. The lymphangiogenic marker and lymphatic vessels in tumour tissues were also assessed using quantitative PCR and immunohistochemistry, respectively. In the mice tumour models, infusion of rhHGF significantly increased the levels of podoplanin and LYVE-1 in the tumour (p=0.05 for podoplanin and p<0.05 for LYVE-1 vs. without HGF in the prostate tumour model, p<0.05 for podoplanin and p<0.01 for LYVE-1 vs. without HGF for the breast tumour model; p<0.05 for podoplanin and p<0.01 for LYVE-1 vs. without HGF in the breast tumour model). The increased level of LYVE-1 transcript was supported by an increase in the number of LYVE-1-positive lymphatic vessels in tumours, using immunohistochemical analysis. Co-injection of MRC5 cells also increased the levels of LYVE-1 and number of LYVE-1-positive vessels in tumour tissues. The effects of HGF and MRC5 were significantly reduced by the HGF antagonist, NK4. In the in vitro models, rhHGF significantly increased the level of both podoplanin and LYVE-1, as shown by quantitative PCR analysis. Hepatocyte growth factor has potential lymphangiogenic activities, and this may have important implications in the nodal spread of cancer cells.

Related Articles

Journal Cover

October 2005
Volume 16 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Jiang WG, Davies G, Martin TA, Parr C, Watkins G, Mansel RE and Mason MD: The potential lymphangiogenic effects of hepatocyte growth factor/scatter factor in vitro and in vivo. Int J Mol Med 16: 723-728, 2005.
APA
Jiang, W.G., Davies, G., Martin, T.A., Parr, C., Watkins, G., Mansel, R.E., & Mason, M.D. (2005). The potential lymphangiogenic effects of hepatocyte growth factor/scatter factor in vitro and in vivo. International Journal of Molecular Medicine, 16, 723-728. https://doi.org/10.3892/ijmm.16.4.723
MLA
Jiang, W. G., Davies, G., Martin, T. A., Parr, C., Watkins, G., Mansel, R. E., Mason, M. D."The potential lymphangiogenic effects of hepatocyte growth factor/scatter factor in vitro and in vivo". International Journal of Molecular Medicine 16.4 (2005): 723-728.
Chicago
Jiang, W. G., Davies, G., Martin, T. A., Parr, C., Watkins, G., Mansel, R. E., Mason, M. D."The potential lymphangiogenic effects of hepatocyte growth factor/scatter factor in vitro and in vivo". International Journal of Molecular Medicine 16, no. 4 (2005): 723-728. https://doi.org/10.3892/ijmm.16.4.723