Regular Article
Glioma Inhibition by HGF/NK2, an Antagonist of Scatter Factor/Hepatocyte Growth Factor

https://doi.org/10.1006/bbrc.2000.2935Get rights and content
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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 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.

Keywords

SF/HGF
c-met
gene therapy
invasion
angiogenesis
malignancy

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1

To whom correspondence should be addressed at Kennedy Krieger Research Institute, 707 N. Broadway, Baltimore, MD 21205. Fax: (410) 502-8093. E-mail: [email protected].