Abstract
Activation of the formylpeptide receptor (FPR), a G-protein-coupled receptor, by its chemotactic peptide ligand N-formylmethionyl-leucyl-phenylalanine (fMLF) promotes the directional migration and survival of human glioblastoma cells. fMLF also stimulates glioblastoma cells to produce biologically active VEGF, an important angiogenic factor involved in tumor progression. In this study, we examined the capacity of FPR to regulate the production of another angiogenic factor, the chemokine IL-8 (CXCL8), in addition to its demonstrated ability to induce VEGF secretion by malignant glioma cells. We showed that the human glioblastoma cell line U87 secreted considerable levels of IL-8 (CXCL8) upon stimulation by the FPR agonist peptide fMLF. Tumor cells transfected with small interference (si)RNA targeting FPR failed to produce IL-8 as well as VEGF in response to fMLF. Glioblastoma cells bearing FPR siRNA exhibited reduced rate of tumorigenicity in nude mice and tumors formed by such tumor cells showed less active angiogenesis and lower level expression of both IL-8 and VEGF. These results suggest that FPR plays an important role in the angiogenesis of human malignant gliomas through increasing the production of angiogenic factors by FPR positive tumor cells.
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Acknowledgments
This project was supported by grants from National Natural Science Foundation of China (NSFC, No. 30670804), the National Key Research Project of Basic Sciences of China (973 project, No. 2006CB708503) and the National High Technology Development Program (863 project, No. 2006 AA02Z475).
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Xiao-Hong Yao and Yi-Fang Ping contributed equally to the study.
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Yao, XH., Ping, YF., Chen, JH. et al. Production of angiogenic factors by human glioblastoma cells following activation of the G-protein coupled formylpeptide receptor FPR. J Neurooncol 86, 47–53 (2008). https://doi.org/10.1007/s11060-007-9443-y
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DOI: https://doi.org/10.1007/s11060-007-9443-y