title: The role of formyl peptide receptor 1 (FPR1) in neuroblastoma tumorigenesis.
abstract: Formyl peptide receptor 1 (FPR1) is a G protein-coupled receptor mainly expressed by the cells of myeloid origin, where it mediates the innate immune response to bacterial formylated peptides. High expression of FPR1 has been detected in various cancers but the function of FPR1 in tumorigenesis is poorly understood.
  
  
  
  Expression of FPR1 in neuroblastoma cell lines and primary tumors was studied using RT-PCR, western blotting, immunofluorescence and immunohistochemistry. Calcium mobilization assays and western blots with phospho-specific antibodies were used to assess the functional activity of FPR1 in neuroblastoma. The tumorigenic capacity of FPR1 was assessed by xenografting of neuroblastoma cells expressing inducible FPR1 shRNA, FPR1 cDNA or control shRNA in nude mice.
  
  
  
  FPR1 is expressed in neuroblastoma primary tumors and cell lines. High expression of FPR1 corresponds with high-risk disease and poor patient survival. Stimulation of FPR1 in neuroblastoma cells using fMLP, a selective FPR1 agonist, induced intracellular calcium mobilization and activation of MAPK/Erk, PI3K/Akt and P38-MAPK signal transduction pathways that were inhibited by using Cyclosporin H, a selective receptor antagonist for FPR1. shRNA knock-down of FPR1 in neuroblastoma cells conferred a delayed xenograft tumor development in nude mice, whereas an ectopic overexpression of FPR1 promoted augmented tumorigenesis in nude mice.
  
  
  
  Our data demonstrate that FPR1 is involved in neuroblastoma development and could represent a therapy option for the treatment of neuroblastoma.
authors.affiliation: Molecular Inflammation Research Group, Department of Medical Biology, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway. igor.v.snapkov@uit.no.
authors.forename: Igor
authors.initials: I
authors.lastname: Snapkov
authors.affiliation: Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Carl Otto
authors.initials: CO
authors.lastname: Öqvist
authors.affiliation: Endocrinology Research Group, Department of Clinical Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.|Department of Medical Biology, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.|Department of Laboratory Medicine, University Hospital of North Norway, Tromsø, Norway.
authors.forename: Yngve
authors.initials: Y
authors.lastname: Figenschau
authors.affiliation: Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Kogner
authors.affiliation: Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
authors.forename: John Inge
authors.initials: JI
authors.lastname: Johnsen
authors.affiliation: Molecular Inflammation Research Group, Department of Medical Biology, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.
authors.forename: Baldur
authors.initials: B
authors.lastname: Sveinbjørnsson
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D002648:Child; D016572:Cyclosporine / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D044042:Receptors, Formyl Peptide / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D014183:Transplantation, Heterologous; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C469986:FPR1 protein, human; D034741:RNA, Small Interfering; D044042:Receptors, Formyl Peptide; D016572:Cyclosporine; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C050025:cyclosporin H; D002118:Calcium
keywords: FPR1; Formyl peptide receptor 1; Inflammation; Neuroblastoma