| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Cancer Biology, Immunology, Cytokines |
Metastasis Research Group, University Department of Surgery, University of Wales College of Medicine, Cardiff CF14 4XN, United Kingdom [W. G. J., S. E. H., C. P., T. A. M., R. E. M.], and Biomedical Research Centre, Osaka University Medical School, Suita, Osaka 565, Japan [K. M., T. N.]
Hepatocyte growth factor (HGF), also known as scatter factor (SF), is known to act on cancer cells as well as endothelial cells and stimulate angiogenesis, thus playing an unwanted role in the development and progression of cancer. The current study examined the effects of a newly discovered HGF variant, NK4, on angiogenesis in vitro. Chemically generated NK4 (from recombinant human HGF/SF) was found to be able to inhibit HGF-induced activation (tyrosine phosphorylation) of the HGF/SF receptor cMET but was itself unable to activate cMET. Furthermore, NK4 was demonstrated to inhibit tubule formation from human umbilical vein endothelial cells that was induced by both HGF/SF and a HGF/SF-producing fibroblast (MRC5). Under the same settings, NK4 failed to increase tubular formation. NK4 had no effects on interleukin 8- and vascular endothelial growth factor-induced tubule formation. Using computer-assisted motion analysis, it was further shown that NK4 inhibited HGF-induced migration of human umbilical vein endothelial cells in a migration assay and in an endothelial wounding assay. These data show that NK4 is a complete antagonist to HGF. It inhibits HGF-induced endothelial movement and tubule formation. Thus, NK4 may have an important bearing on the control of cancer progression through its role in angiogenesis. Additional in vivo studies are warranted.
This article has been cited by other articles:
|
|
 |
|
  L. N. Bell, L. Cai, B. H. Johnstone, D. O. Traktuev, K. L. March, and R. V. Considine A central role for hepatocyte growth factor in adipose tissue angiogenesis Am J Physiol Endocrinol Metab, February 1, 2008; 294(2): E336 - E344. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Siegfried, C. T. Gubish, M. E. Rothstein, P. E. Q. de Oliveira, and L. P. Stabile Signaling Pathways Involved in Cyclooxygenase-2 Induction by Hepatocyte Growth Factor in Non Small-Cell Lung Cancer Mol. Pharmacol., September 1, 2007; 72(3): 769 - 779. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. D. Francone, R. G. Landmann, C.-T. Chen, M. Y. Sun, E. J. Kuntz, Z. Zeng, R. P. Dematteo, P. B. Paty, and M. R. Weiser Novel xenograft model expressing human hepatocyte growth factor shows ligand-dependent growth of c-Met-expressing tumors Mol. Cancer Ther., April 1, 2007; 6(4): 1460 - 1466. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Martens, N.-O. Schmidt, C. Eckerich, R. Fillbrandt, M. Merchant, R. Schwall, M. Westphal, and K. Lamszus A Novel One-Armed Anti-c-Met Antibody Inhibits Glioblastoma Growth In vivo. Clin. Cancer Res., October 15, 2006; 12(20): 6144 - 6152. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Abounader and J. Laterra Scatter factor/hepatocyte growth factor in brain tumor growth and angiogenesis Neuro-oncol, October 1, 2005; 7(4): 436 - 451. [Abstract] [PDF]
|
|
|
|
|
|
M. A. Brockmann, A. Papadimitriou, M. Brandt, R. Fillbrandt, M. Westphal, and K. Lamszus Inhibition of Intracerebral Glioblastoma Growth by Local Treatment with the Scatter Factor/Hepatocyte Growth Factor-Antagonist NK4 Clin. Cancer Res., October 1, 2003; 9(12): 4578 - 4585. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Merkulova-Rainon, P. England, S. Ding, C. Demerens, and G. Tobelem The N-terminal Domain of Hepatocyte Growth Factor Inhibits the Angiogenic Behavior of Endothelial Cells Independently from Binding to the c-met Receptor J. Biol. Chem., September 26, 2003; 278(39): 37400 - 37408. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. G. Jiang, D. Grimshaw, T. A. Martin, G. Davies, C. Parr, G. Watkins, J. Lane, R. Abounader, J. Laterra, and R. E. Mansel Reduction of Stromal Fibroblast-induced Mammary Tumor Growth, by Retroviral Ribozyme Transgenes to Hepatocyte Growth Factor/Scatter Factor and its Receptor, c-MET Clin. Cancer Res., September 15, 2003; 9(11): 4274 - 4281. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. A. Martin, C. Parr, G. Davies, G. Watkins, J. Lane, K. Matsumoto, T. Nakamura, R. E. Mansel, and W. G. Jiang Growth and angiogenesis of human breast cancer in a nude mouse tumour model is reduced by NK4, a HGF/SF antagonist Carcinogenesis, August 1, 2003; 24(8): 1317 - 1323. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ding, T. Merkulova-Rainon, Z. C. Han, and G. Tobelem HGF receptor up-regulation contributes to the angiogenic phenotype of human endothelial cells and promotes angiogenesis in vitro Blood, June 15, 2003; 101(12): 4816 - 4822. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. G. Jiang, D. Grimshaw, J. Lane, T. A. Martin, R. Abounder, J. Laterra, and R. E. Mansel A Hammerhead Ribozyme Suppresses Expression of Hepatocyte Growth Factor/Scatter Factor Receptor c-MET and Reduces Migration and Invasiveness of Breast Cancer Cells Clin. Cancer Res., August 1, 2001; 7(8): 2555 - 2562. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kuba, K. Matsumoto, K. Date, H. Shimura, M. Tanaka, and T. Nakamura HGF/NK4, a Four-Kringle Antagonist of Hepatocyte Growth Factor, Is an Angiogenesis Inhibitor that Suppresses Tumor Growth and Metastasis in Mice Cancer Res., December 1, 2000; 60(23): 6737 - 6743. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
