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

Christopher Guerin, Carey Luddy, Roger Abounader, Bachchu Lal, John Laterra

Research output: Contribution to journalArticlepeer-review

Abstract

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 ~ 20-fold less clonogenic in soft agar and ~ 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 ~ 50-fold smaller than controls at 21 days postimplantation 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. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)287-293
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume273
Issue number1
DOIs
StatePublished - Jun 24 2000

Keywords

  • Angiogenesis
  • Gene therapy
  • Invasion
  • Malignancy
  • SF/HGF
  • c-met

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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