| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
ABL-Basic Research Program, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, Maryland 21702
The met protooncogene tyrosine kinase receptor (Met) and its ligand, hepatocyte growth factor/scatter factor (HGF/SF), ordinarily constitute a paracrine signaling system in which cells of mesenchymal origin produce the lignad, which binds to the receptor that is predominantly expressed in cells of epithelial origin. However, mouse NIH/3T3 fibroblasts overexpressing Met induce tumor formation in nude mice via an autocrine mechanism (S. Rong et al., Mol. Cell. Biol., 12: 5152–5158, 1992). In this study, we report that human cell lines established from various sarcomas express high levels of activated Met receptor. HGF/SF is also detected in the human sarcoma cell lines but at a reduced level when compared to primary fibroblasts. These properties, high Met expression and reduced ligand levels, are indistinguishable from the properties of NIH/3T3 tumor explant cells overexpressing Met (S. Rong et al., Mol. Cell. Biol., 12: 5152–5158, 1992; S. Rong et al., Cell Growth & Differ., 4: 563–569, 1993). Moreover, paraffin-embedded sections of primary tumors from human osteosarcomas, chondrosarcomas, and leiomyosarcoma stain intensely for Met and/or HGF/SF and display extensive tumor cell heterogeneity with regard to both paracrine and autocrine stimulation. On the basis of these findings, we propose that Met-HGF/SF autocrine signaling may contribute to the tumorigenic process in human sarcomas.
1 Research sponsored by the National Cancer Institute, DHHS, under contract NO1-CO-74101 with ABL. The contents of this publication do not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.
2 To whom requests for reprints should be addressed.
Received 10/ 5/93. Accepted 10/11/93.
This article has been cited by other articles:
|
|
 |
|
  C.-F. Gao, Q. Xie, Y.-W. Zhang, Y. Su, P. Zhao, B. Cao, K. Furge, J. Sun, K. Rex, T. Osgood, et al. Therapeutic potential of hepatocyte growth factor/scatter factor neutralizing antibodies: Inhibition of tumor growth in both autocrine and paracrine hepatocyte growth factor/scatter factor:c-Met-driven models of leiomyosarcoma Mol. Cancer Ther., October 1, 2009; 8(10): 2803 - 2810. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Fieten, B. Spee, J. IJzer, M. J. Kik, L. C. Penning, and J. Kirpensteijn Expression of Hepatocyte Growth Factor and the Proto-oncogenic Receptor c-Met in Canine Osteosarcoma Vet. Pathol., September 1, 2009; 46(5): 869 - 877. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Zhao, T. Grabinski, C. Gao, R. S. Skinner, T. Giambernardi, Y. Su, E. Hudson, J. Resau, M. Gross, G. F. Vande Woude, et al. Identification of a Met-Binding Peptide from a Phage Display Library Clin. Cancer Res., October 15, 2007; 13(20): 6049 - 6055. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-F. Gao, Q. Xie, Y.-L. Su, J. Koeman, S. K. Khoo, M. Gustafson, B. S. Knudsen, R. Hay, N. Shinomiya, and G. F. V. Woude Proliferation and invasion: Plasticity in tumor cells PNAS, July 26, 2005; 102(30): 10528 - 10533. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-S. Lin, G. J. Berry, W. E. Fee Jr, D. J. Terris, and Z. Sun Identification of Tyrosine Kinases Overexpressed in Head and Neck Cancer Arch Otolaryngol Head Neck Surg, March 1, 2004; 130(3): 311 - 316. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Yoshida, T. Harada, M. Mitsunari, T. Iwabe, Y. Sakamoto, S. Tsukihara, Y. Iba, S. Horie, and N. Terakawa Hepatocyte Growth Factor/Met System Promotes Endometrial and Endometriotic Stromal Cell Invasion via Autocrine and Paracrine Pathways J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 823 - 832. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Imaizumi, H. Murota, S. Kanda, Y. Hishikawa, T. Koji, T. Taguchi, Y. Tanaka, Y. Yamada, S. Ikeda, T. Kohno, et al. Expression of the c-Met Proto-Oncogene and Its Possible Involvement in Liver Invasion in Adult T-cell Leukemia Clin. Cancer Res., January 1, 2003; 9(1): 181 - 187. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Pediaditakis, S. P. S. Monga, W. M. Mars, and G. K. Michalopoulos Differential Mitogenic Effects of Single Chain Hepatocyte Growth Factor (HGF)/Scatter Factor and HGF/NK1 following Cleavage by Factor Xa J. Biol. Chem., April 12, 2002; 277(16): 14109 - 14115. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-N. Qian, X. Guo, B. Cao, E. J. Kort, C.-C. Lee, J. Chen, L.-M. Wang, W.-Y. Mai, H.-Q. Min, M.-H. Hong, et al. Met Protein Expression Level Correlates with Survival in Patients with Late-stage Nasopharyngeal Carcinoma Cancer Res., January 1, 2002; 62(2): 589 - 596. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Cao, Y. Su, M. Oskarsson, P. Zhao, E. J. Kort, R. J. Fisher, L.-M. Wang, and G. F. Vande Woude Neutralizing monoclonal antibodies to hepatocyte growth factor/scatter factor (HGF/SF) display antitumor activity in animal models PNAS, June 19, 2001; 98(13): 7443 - 7448. [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]
|
|
|
|
 |
|
 M. C. Briggs, I. Grierson, P. Hiscott, and J. A. Hunt Active Scatter Factor (HGF/SF) in Proliferative Vitreoretinal Disease Invest. Ophthalmol. Vis. Sci., September 1, 2000; 41(10): 3085 - 3094. [Abstract] [Full Text]
|
|
|
|
 |
|
 D. M. Kamikura, H. Khoury, C. Maroun, M. A. Naujokas, and M. Park Enhanced Transformation by a Plasma Membrane-Associated Met Oncoprotein: Activation of a Phosphoinositide 3'-Kinase-Dependent Autocrine Loop Involving Hyaluronic Acid and CD44 Mol. Cell. Biol., May 15, 2000; 20(10): 3482 - 3496. [Abstract] [Full Text]
|
|
|
|
|
|
T. Otsuka, J. Jakubczak, W. Vieira, D. P. Bottaro, D. Breckenridge, W. J. Larochelle, and G. Merlino Disassociation of Met-Mediated Biological Responses In Vivo: the Natural Hepatocyte Growth Factor/Scatter Factor Splice Variant NK2 Antagonizes Growth but Facilitates Metastasis Mol. Cell. Biol., March 15, 2000; 20(6): 2055 - 2065. [Abstract] [Full Text]
|
|
|
|
 |
|
 V. Wallenius, M. Hisaoka, K. Helou, G. Levan, N. Mandahl, J. M. Meis-Kindblom, L.-G. Kindblom, and J.-O. Jansson Overexpression of the Hepatocyte Growth Factor (HGF) Receptor (Met) and Presence of a Truncated and Activated Intracellular HGF Receptor Fragment in Locally Aggressive/Malignant Human Musculoskeletal Tumors Am. J. Pathol., March 1, 2000; 156(3): 821 - 829. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. Taylor, E. Hudson, J. H. Resau, and G. F. Vande Woude Regulation of P311 Expression by Met-Hepatocyte Growth Factor/Scatter Factor and the Ubiquitin/Proteasome System J. Biol. Chem., February 11, 2000; 275(6): 4215 - 4219. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Abounader, S. Ranganathan, B. Lal, K. Fielding, A. Book, H. Dietz, P. Burger, and J. Laterra Reversion of Human Glioblastoma Malignancy by U1 Small Nuclear RNA/Ribozyme Targeting of Scatter Factor/Hepatocyte Growth Factor and c-met Expression J Natl Cancer Inst, September 15, 1999; 91(18): 1548 - 1556. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Koochekpour, M. Jeffers, P. H. Wang, C. Gong, G. A. Taylor, L. M. Roessler, R. Stearman, J. R. Vasselli, W. G. Stetler-Stevenson, W. G. Kaelin Jr., et al. The von Hippel-Lindau Tumor Suppressor Gene Inhibits Hepatocyte Growth Factor/Scatter Factor-Induced Invasion and Branching Morphogenesis in Renal Carcinoma Cells Mol. Cell. Biol., September 1, 1999; 19(9): 5902 - 5912. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. A. Lubensky, L. Schmidt, Z. Zhuang, G. Weirich, S. Pack, N. Zambrano, M. M. Walther, P. Choyke, W. M. Linehan, and B. Zbar Hereditary and Sporadic Papillary Renal Carcinomas with c-met Mutations Share a Distinct Morphological Phenotype Am. J. Pathol., August 1, 1999; 155(2): 517 - 526. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D.-W. Seol, Q. Chen, M. L. Smith, and R. Zarnegar Regulation of the c-met Proto-oncogene Promoter by p53 J. Biol. Chem., February 5, 1999; 274(6): 3565 - 3572. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Ronen, R. T. Altstock, M. Firon, L. Mittelman, T. Sobe, J. H. Resau, G. F. Vande Woude, and I. Tsarfaty Met-HGF/SF Mediates Growth Arrest and Differentiation in T47D Breast Cancer Cells Cell Growth Differ., February 1, 1999; 10(2): 131 - 140. [Abstract] [Full Text]
|
|
|
|
|
|
A. W. Bell, J.-G. Jiang, Q. Chen, Y. Liu, and R. Zarnegar The Upstream Regulatory Regions of the Hepatocyte Growth Factor Gene Promoter Are Essential for Its Expression in Transgenic Mice J. Biol. Chem., March 20, 1998; 273(12): 6900 - 6908. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Jakubczak, W. J. Larochelle, and G. Merlino NK1, a Natural Splice Variant of Hepatocyte Growth Factor/Scatter Factor, Is a Partial Agonist In Vivo Mol. Cell. Biol., March 1, 1998; 18(3): 1275 - 1283. [Abstract] [Full Text]
|
|
|
|
|
|
M. Lyon, J. A. Deakin, H. Rahmoune, D. G. Fernig, T. Nakamura, and J. T. Gallagher Hepatocyte Growth Factor/Scatter Factor Binds with High Affinity to Dermatan Sulfate J. Biol. Chem., January 2, 1998; 273(1): 271 - 278. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Anastasi, S. Giordano, O. Sthandier, G. Gambarotta, R. Maione, P. Comoglio, and P. Amati A Natural Hepatocyte Growth Factor/Scatter Factor Autocrine Loop in Myoblast Cells and the Effect of the Constitutive Met Kinase Activation on Myogenic Differentiation J. Cell Biol., June 2, 1997; 137(5): 1057 - 1068. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Takayama, W. J. LaRochelle, R. Sharp, T. Otsuka, P. Kriebel, M. Anver, S. A. Aaronson, and G. Merlino Diverse tumorigenesis associated with aberrant development in mice overexpressing hepatocyte growth factor/scatter factor PNAS, January 21, 1997; 94(2): 701 - 706. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Y. Ljubimova, L. M. Petrovic, S. E. Wilson, S. A. Geller, and A. A. Demetriou Expression of HGF, Its Receptor c-met, c-myc, and Albumin in Cirrhotic and Neoplastic Human Liver Tissue J. Histochem. Cytochem., January 1, 1997; 45(1): 79 - 88. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Borset, E. Lien, T. Espevik, E. Helseth, A. Waage, and A. Sundan Concomitant Expression of Hepatocyte Growth Factor/Scatter Factor and the Receptor c-MET in Human Myeloma Cell Lines J. Biol. Chem., October 4, 1996; 271(40): 24655 - 24661. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I Tsarfaty, S Rong, J. Resau, S Rulong, P. da Silva, and G. Vande Woude The Met proto-oncogene mesenchymal to epithelial cell conversion Science, January 7, 1994; 263(5143): 98 - 101. [Abstract] [PDF]
|
|
|
|
 |
|
 S. Rong and G.F. Vande Woude Autocrine Mechanism for met Proto-oncogene Tumorigenicity Cold Spring Harb Symp Quant Biol, January 1, 1994; 59(0): 629 - 636. [Abstract] [PDF]
|
|
| 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 |
