Investigation o the factors involved in proliferation and angiogenesis of malignant glioma : study on heparin-binding EGF-like growth factor (HB-EGF)

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The objective of the present study is to investigate the role of heparin-binding EGF-like growth factor(HB-EGF), which is highly expressed in glioma cells, in progression of malignant glioma, focusing on its effect on the angiogenesis and cellular infiltration.(A)Involvement of HB-EGF in proliferation of glioma cellsApplying recombinant HB-EGF(rHB-EGF)to glioma cells facilitated the proliferation and DNA synthesis of those cells. Applying specific antibody against HB-EGF to glioma cells inhibited proliferation down to 70% of the control. These results suggested that HB-EGF is strongly involved in proliferation of glioma as an autocrine proliferative factor.(B)Involvement of HB-EGF in angiogenesis of gliomaApplying rHB-EGF to cultured glioma cells induced expression of vascular endothelial growth factor(VEGF)mRNA,which was evaluated by Northern hybridization method. The effect was initiated at 3 hours after the application of rHB-EGF and was dose-dependent. Secretion of VEGF protein, which was evaluated by Western blotting anslysis, was also increased by application of rHB-EGF.The study demonstrated that HB-EGF is not only essential for proliferation of glioma cells but also contributes to angiogenesis of glioma via upregulation of VEGF.