© 2005 by the Society for Neuro-Oncology
Scatter factor/hepatocyte growth factor in brain tumor growth and angiogenesis
Departments of Neurology (R.A., J.L.), Oncology (R.A., J.L.), and Neuroscience (J.L.), The Johns Hopkins University School of Medicine and The Kennedy Krieger Research Institute, Baltimore, MD 21205, USA
2 Address correspondence to John Laterra, Kennedy Krieger Research Institute, 707 N. Broadway, Baltimore, MD 21205, USA (Laterra{at}kennedykrieger.org).
 |
Abstract |
|---|
The multifunctional growth factor scatter factor/hepatocyte growth factor (SF/HGF) and its receptor tyrosine kinase c-Met have emerged as key determinants of brain tumor growth and angiogenesis. SF/HGF and c-Met are expressed in brain tumors, the expression levels frequently correlating with tumor grade, tumor blood vessel density, and poor prognosis. Overexpression of SF/HGF and/or c-Met in brain tumor cells enhances their tumorigenicity, tumor growth, and tumor-associated angiogenesis. Conversely, inhibition of SF/HGF and c-Met in experimental tumor xenografts leads to inhibition of tumor growth and tumor angiogenesis. SF/HGF is expressed and secreted mainly by tumor cells and acts on c-Met receptors that are expressed in tumor cells and vascular endothelial cells. Activation of c-Met leads to induction of proliferation, migration, and invasion and to inhibition of apoptosis in tumor cells as well as in tumor vascular endothelial cells. Activation of tumor endothelial c-Met also induces extracellular matrix degradation, tubule formation, and angiogenesis in vivo. SF/HGF induces brain tumor angiogenesis directly through only partly known mechanisms and indirectly by regulating other angiogenic pathways such as VEGF. Different approaches to inhibiting SF/HGF and c-Met have been recently developed. These include receptor antagonism with SF/HGF fragments such as NK4, SF/HGF, and c-Met expression inhibition with U1snRNA/ribozymes; competitive ligand binding with soluble Met receptors; neutralizing antibodies to SF/HGF; and small molecular tyrosine kinase inhibitors. Use of these inhibitors in experimental tumor models leads to inhibition of tumor growth and angiogenesis. In this review, we summarize current knowledge of how the SF/HGF:c-Met pathway contributes to brain tumor malignancy with a focus on glioma angiogenesis.
Received January 12, 2005; Accepted March 16, 2005
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  Z. Pei, P. Sun, P. Huang, B. Lal, J. Laterra, and P. A. Watkins Acyl-CoA Synthetase VL3 Knockdown Inhibits Human Glioma Cell Proliferation and Tumorigenicity Cancer Res., December 15, 2009; 69(24): 9175 - 9182. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Li, F. Guessous, Y. Zhang, C. DiPierro, B. Kefas, E. Johnson, L. Marcinkiewicz, J. Jiang, Y. Yang, T. D. Schmittgen, et al. MicroRNA-34a Inhibits Glioblastoma Growth by Targeting Multiple Oncogenes Cancer Res., October 1, 2009; 69(19): 7569 - 7576. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Provencal, D. Labbe, R. Veitch, D. Boivin, G.-E. Rivard, H. Sartelet, Y. Robitaille, D. Gingras, and R. Beliveau c-Met activation in medulloblastoma induces tissue factor expression and activity: effects on cell migration Carcinogenesis, July 1, 2009; 30(7): 1089 - 1096. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Lou, Q. Zhou, Y. Yin, C. Zhou, and Y. Shen Inhibition of the met receptor tyrosine kinase signaling enhances the chemosensitivity of glioma cell lines to CDDP through activation of p38 MAPK pathway Mol. Cancer Ther., May 1, 2009; 8(5): 1126 - 1136. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. H. Lee, M. J. Seo, A. A. Pulin, C. A. Gregory, J. Ylostalo, and D. J. Prockop The CD34-like protein PODXL and {alpha}6-integrin (CD49f) identify early progenitor MSCs with increased clonogenicity and migration to infarcted heart in mice Blood, January 22, 2009; 113(4): 816 - 826. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. N. Kongkham, P. A. Northcott, Y. S. Ra, Y. Nakahara, T. G. Mainprize, S. E. Croul, C. A. Smith, M. D. Taylor, and J. T. Rutka An Epigenetic Genome-Wide Screen Identifies SPINT2 as a Novel Tumor Suppressor Gene in Pediatric Medulloblastoma Cancer Res., December 1, 2008; 68(23): 9945 - 9953. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Trapp, G. Kogler, A. El-Khattouti, R. V. Sorg, M. Besselmann, M. Focking, C. P. Buhrle, I. Trompeter, J. C. Fischer, and P. Wernet Hepatocyte Growth Factor/c-MET Axis-mediated Tropism of Cord Blood-derived Unrestricted Somatic Stem Cells for Neuronal Injury J. Biol. Chem., November 21, 2008; 283(47): 32244 - 32253. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Binning, T. Niazi, C. A. Pedone, B. Lal, C. G. Eberhart, K. J. Kim, J. Laterra, and D. W. Fults Hepatocyte Growth Factor and Sonic Hedgehog Expression in Cerebellar Neural Progenitor Cells Costimulate Medulloblastoma Initiation and Growth Cancer Res., October 1, 2008; 68(19): 7838 - 7845. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. E. Reznik, Y. Sang, Y. Ma, R. Abounader, E. M. Rosen, S. Xia, and J. Laterra Transcription-Dependent Epidermal Growth Factor Receptor Activation by Hepatocyte Growth Factor Mol. Cancer Res., January 1, 2008; 6(1): 139 - 150. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. B. Hoelzinger, T. Demuth, and M. E. Berens Autocrine Factors That Sustain Glioma Invasion and Paracrine Biology in the Brain Microenvironment J Natl Cancer Inst, November 7, 2007; 99(21): 1583 - 1593. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Matteucci, E. Ridolfi, P. Maroni, P. Bendinelli, and M. A. Desiderio c-Src/Histone Deacetylase 3 Interaction Is Crucial for Hepatocyte Growth Factor Dependent Decrease of CXCR4 Expression in Highly Invasive Breast Tumor Cells Mol. Cancer Res., August 1, 2007; 5(8): 833 - 845. [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]
|
|