title: Microenvironment involved in FPR1 expression by human glioblastomas.
abstract: Formyl peptide receptor 1 (FPR1) activity in U87 glioblastoma (GBM) cells contributes to tumor cell motility. The present study aimed to evaluate the FPR1 expression in human GBM, the possibility to elicit agonist induced FPR1 activation of GBM cells and inhibit this activation with chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS). Immunohistochemistry was used to assess FPR1 expression in GBM patient samples, which was present in all 178 samples. Also FPR1 mRNA levels measured with quantitative PCR, could be detected in all 25 GBM patient samples tested. Activation of FPR1 in U87 cells, as measured by human mitochondrial-derived agonists, increased calcium mobilization, AKT and ERK1/2 phosphorylation, and ligand-induced migration. Inhibition of all responses could be achieved with CHIPS. Eight early passage human Groningen Glioma (GG) cell lines, isolated from primary GBM tissue were screened for the presence of FPR1. FPR1 mRNA and protein expression as well as receptor activation could not be detected in any of these early passage GG cell lines. However FPR1 was present in ex vivo tumors formed by the same GG cell lines after being implanted in mouse brains. FPR1 is highly expressed in human GBM specimens, it can be activated by human mitochondrial-derived agonists in U87 and inhibited with CHIPS. FPR1 cannot be detected in early passage GG cell lines in vitro, however when engrafted in the mouse brain these cells show FPR1 expression. These results suggest a role of the brain microenvironment in FPR1 expression in GBM.
authors.affiliation: Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, P.O. Box 30001, 9700, RB, Groningen, The Netherlands.
authors.forename: J C
authors.initials: JC
authors.lastname: Boer
authors.forename: D M S
authors.initials: DM
authors.lastname: van Marion
authors.forename: J V
authors.initials: JV
authors.lastname: Joseph
authors.forename: N M
authors.initials: NM
authors.lastname: Kliphuis
authors.forename: H
authors.initials: H
authors.lastname: Timmer-Bosscha
authors.forename: J A G
authors.initials: JA
authors.lastname: van Strijp
authors.forename: E G E
authors.initials: EG
authors.lastname: de Vries
authors.forename: W F A
authors.initials: WF
authors.lastname: den Dunnen
authors.forename: F A E
authors.initials: FA
authors.lastname: Kruyt
authors.forename: A M E
authors.initials: AM
authors.lastname: Walenkamp
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D005455:Fluorescent Antibody Technique; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D007376:Interleukin-2 / Q000502:physiology*; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D044042:Receptors, Formyl Peptide / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D059016:Tumor Microenvironment
chemical_list: D014408:Biomarkers, Tumor; C469986:FPR1 protein, human; D007376:Interleukin-2; D012333:RNA, Messenger; D044042:Receptors, Formyl Peptide