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

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

Research output: Contribution to journalArticle

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

Fingerprint

Hepatocyte Growth Factor
Glioma
Gene transfer
Tumors
Cells
Cell Line
Genes
Phenotype
Neoplasms
Biological Therapy
Cell growth
Glioblastoma
Heterografts
Brain Neoplasms
Agar
Brain
Intercellular Signaling Peptides and Proteins
Complementary DNA
Cytokines
Growth

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Glioma inhibition by HGF/NK2, an antagonist of scatter factor/hepatocyte growth factor. / Guerin, Christopher; Luddy, Carey; Abounader, Roger; Lal, Bachchu; Laterra, John J.

In: Biochemical and Biophysical Research Communications, Vol. 273, No. 1, 24.06.2000, p. 287-293.

Research output: Contribution to journalArticle

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