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. 2009 Oct;8(10):2803-10. doi: 10.1158/1535-7163.MCT-09-0125.


Hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, c-Met, have been implicated in the growth and progression of a variety of solid human tumors. Thus, inhibiting HGF/SF:c-Met signaling may provide a novel therapeutic approach for treating human tumors. We have generated and characterized fully human monoclonal antibodies that bind to and neutralize human HGF/SF. In this study, we tested the effects of the investigational, human anti-human HGF/SF monoclonal antibody, AMG 102, and a mixture of mouse anti-human HGF/SF monoclonal antibodies (Amix) on HGF/SF-mediated cell migration, proliferation, and invasion in vitro. Both agents had high HGF/SF-neutralizing activity in these cell-based assays. The HGF/SF:c-Met pathway has been implicated in the growth of sarcomas; thus, we also investigated the effect of AMG 102 on the growth of human leiomyosarcoma (SK-LMS-1) in HGF/SF transgenic C3H severe combined immunodeficient mice engineered to express high levels of human HGF/SF, as well as tumor growth of an autocrine variant of the SK-LMS-1 cell line (SK-LMS-1TO) in nude mice. The results indicate that interrupting autocrine and/or paracrine HGF/SF:c-Met signaling with AMG 102 has profound antitumor effects. These findings suggest that blocking HGF/SF:c-Met signaling may provide a potent intervention strategy to treat patients with HGF/SF:c-Met-dependent tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / pharmacology
  • Antibodies, Neutralizing / therapeutic use*
  • Autocrine Communication* / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Fibrinolysin / metabolism
  • Hepatocyte Growth Factor / immunology*
  • Humans
  • Leiomyosarcoma / drug therapy*
  • Leiomyosarcoma / immunology
  • Leiomyosarcoma / pathology*
  • Ligands
  • Mice
  • Mice, Transgenic
  • Models, Immunological
  • Neoplasm Invasiveness
  • Paracrine Communication* / drug effects
  • Proto-Oncogene Proteins c-met / metabolism*
  • Signal Transduction / drug effects
  • Urokinase-Type Plasminogen Activator / metabolism
  • Xenograft Model Antitumor Assays


  • Antibodies, Neutralizing
  • Ligands
  • Hepatocyte Growth Factor
  • Proto-Oncogene Proteins c-met
  • Fibrinolysin
  • Urokinase-Type Plasminogen Activator