Glioma inhibition by HGF/NK2, an antagonist of scatter factor/hepatocyte growth factor

Biochem Biophys Res Commun. 2000 Jun 24;273(1):287-93. doi: 10.1006/bbrc.2000.2935.


Strategies that antagonize growth factor signaling are attractive candidates for the biological therapy of brain tumors. HGF/NK2 is a secreted truncated splicing variant and potential antagonist of scatter factor/hepatocyte growth factor (SF/HGF), a multifunctional cytokine involved in the malignant progression of solid tumors including glioblastoma. U87 human malignant glioma cells that express an autocrine SF/HGF stimulatory loop were transfected with the human HGF/NK2 cDNA and clonal cell lines that secrete high levels of HGF/NK2 protein (U87-NK2) were isolated. The effects of HGF/NK2 gene transfer on the U87 malignant phenotype were examined. HGF/NK2 gene transfer had no effect on 2-dimensional anchorage-dependent cell growth. In contrast, U87-NK2 cell lines were approximately 20-fold less clonogenic in soft agar and approximately 4-fold less migratory than control-transfected cell lines. Intracranial tumor xenografts derived from U87-NK2 cells grew much slower than controls. U87-NK2 tumors were approximately 50-fold smaller than controls at 21 days post-implantation and HGF/NK2 gene transfer resulted in a trend toward diminished tumorigenicity. This report shows that the predominant effect of transgenic HGF/NK2 overexpression by glioma cells that are autocrine for SF/HGF stimulation is to inhibit their malignant phenotype.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Agar / metabolism
  • Alternative Splicing / genetics*
  • Animals
  • Autocrine Communication
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Cell Adhesion
  • Cell Division
  • Cell Movement
  • Cell Transformation, Neoplastic / pathology
  • Gene Transfer Techniques
  • Glioma / drug therapy
  • Glioma / genetics
  • Glioma / metabolism
  • Glioma / pathology*
  • Hepatocyte Growth Factor / antagonists & inhibitors*
  • Hepatocyte Growth Factor / chemistry
  • Hepatocyte Growth Factor / genetics
  • Hepatocyte Growth Factor / physiology*
  • Humans
  • Mice
  • Mice, SCID
  • Molecular Weight
  • Neoplasm Transplantation / pathology
  • Phenotype
  • Transfection
  • Transplantation, Heterologous / pathology
  • Tumor Cells, Cultured


  • Hepatocyte Growth Factor
  • Agar