Abstract
A108
Vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) are produced by tumor cells and promote tumor angiogenesis. Our previous studies showed that activation of formylpeptide receptor (FPR), a G-protein-coupled receptor, contributes to the motility and growth of malignant glioma cells as well as angiogenesis. In the present study, we aimed to investigate the role of FPR in the production of angiogenic factors, VEGF and IL-8, in human glioblastoma cells. We found that the expression levels of VEGF and IL-8 in human glioma tissues of various malignancies were correlated with the expression of FPR and microvessel densities (MVD), and FPR stimulated with fMLF induced the production of VEGF and IL-8 by both glioma cell lines and primary glioma cells, with more significant effects on IL-8. There was no interaction effect between VEGF and IL-8 in the cultured cells. Target-specific siRNA-induced formylpeptide (FPR) knockdown completely neutralized the increase of the two factor secretion that was mediated by FPR, and reduced the growth, angiogenesis and expression of VEGF and IL-8 of the implanted tumor growth in mice, demonstrating the essential role of FPR-mediated VEGF and IL-8 production in glioma progression. The results showed that FPR/fMLF up-regulates the expression of VEGF and IL-8 in human glioblastoma cells which in turn may contribute to the angiogenesis of malignant glioma.
[Fifth AACR International Conference on Frontiers in Cancer Prevention Research, Nov 12-15, 2006]