Production of angiogenic factors by human glioblastoma cells following activation of the G-protein coupled formylpeptide receptor FPR.
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.
Yao
Xiao-Hong
XH
Institute of Pathology, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
Ping
Yi-Fang
YF
Chen
Jian-Hong
JH
Chen
Dai-Lun
DL
Xu
Cheng-Ping
CP
Zheng
Jiang
J
Wang
Ji Ming
JM
Bian
Xiu-Wu
XW
D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048988:Corneal Surgery, Laser / Q000379:methods; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000627:therapeutic use; D044042:Receptors, Formyl Peptide / Q000378:metabolism*; D013778:Tetrazolium Salts; D013844:Thiazoles; D013997:Time Factors; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D043925:Angiogenesis Inducing Agents; D016209:Interleukin-8; D044042:Receptors, Formyl Peptide; D013778:Tetrazolium Salts; D013844:Thiazoles; D042461:Vascular Endothelial Growth Factor A; D009240:N-Formylmethionine Leucyl-Phenylalanine; C022616:thiazolyl blue