Ectopic expression of vascular endothelial growth factor (VEGF) by C6 glioma cells does not increase tumour growth in vivo despite an increase in angiogenesis

Abstract

The growth of solid tumours is dependent on a number of processes and one of the most important is angiogenesis. Several growth factors have been demonstrated to have angiogenic activity, yet only one factor, vascular endothelial growth factor (VEGF) appears to act specifically as a mitogen on endothelial cells. To date, two receptors for VEGF have been characterised, VEGF-R1 and VEGF-R2 which are expressed on endothelial cells. However, the precise role(s) of each of these receptors in the process of tumour neovascularisation is not entirely clear. It has been demonstrated that the inhibition of VEGF expression in rat C6 glioma cells results in the suppression of tumour growth in vivo. Therefore, it was of interest to determine whether an increase in VEGF expression in C6 cells would promote an accelerated tumourigenicity in vivo. In order to address the role(s) of VEGF in tumour angiogenesis and growth, we have generated rat C6 glioma cells that express VEGF(165) in constitutively high levels and investigated their growth properties in vitro and in vivo as well as the vasculature they generate in vivo. The cell lines expressing VEGF are morphologically different to the parental C6 cells and grow at a slower rate ia vitro. In vivo, the VEGF expressing rumours also grew slowly, were highly vascularised and contained varying degrees of necrosis and eosinophilic infiltrate. Therefore, VEGF appears to be essential for neovascularisation of tumours but this process does not result in a more rapid tumour growth rate of C6 cells and is not sufficient in preventing the onset of tumour necrosis nor an eosinophilic immune response.