title: Involvement of CD9 and PDGFR in migration is evolutionarily conserved from Drosophila glia to human glioma.
abstract: Platelet-derived growth factor receptor (PDGFR) signaling plays an important role in the biology of malignant gliomas. To investigate mechanisms modulating PDGFR signaling in gliomagenesis, we employed a Drosophila glioma model and genetic screen to identify genes interacting with Pvr, the fly homolog of PDGFRs. Glial expression of constitutively activated Pvr (λPvr) led to glial over migration and lethality at late larval stage. Among 3316 dsRNA strains crossed against the tester strain, 128 genes shifted lethality to pupal stage, including tetraspanin 2A (tsp2A). In a second step knockdown of all Drosophila tetraspanins was investigated. Of all tetraspanin dsRNA strains only knockdown of tsp2A partially rescued the Pvr-induced phenotype. Human CD9 (TSPAN29/MRP-1), a close homolog of tsp2A, was found to be expressed in glioma cell lines A172 and U343MG as well as in the majority of glioblastoma samples (16/22, 73 %). Furthermore, in situ proximity ligation assay revealed close association of CD9 with PDGFR α and β. In U343MG cells, knockdown of CD9 blocked PDGF-BB stimulated migration. In conclusion, modulation of PDGFR signaling by CD9 is evolutionarily conserved from Drosophila glia to human glioma and plays a role in glia migration.
authors.affiliation: Institute of Neuropathology, University Hospital Münster, Pottkamp 2, 48129, Münster, Germany. jeibmann@uni-muenster.de.
authors.forename: Astrid
authors.initials: A
authors.lastname: Jeibmann
authors.affiliation: Institute of Neuropathology, University Hospital Münster, Pottkamp 2, 48129, Münster, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Halama
authors.affiliation: Institute of Neuropathology, University Hospital Münster, Pottkamp 2, 48129, Münster, Germany.|Institute of Neurobiology, University Münster, Münster, Germany.
authors.forename: Hanna Theresa
authors.initials: HT
authors.lastname: Witte
authors.affiliation: Institute of Neurobiology, University Münster, Münster, Germany.
authors.forename: Su Na
authors.initials: SN
authors.lastname: Kim
authors.affiliation: Institute of Neuropathology, University Hospital Münster, Pottkamp 2, 48129, Münster, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Eikmeier
authors.affiliation: Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Koos
authors.affiliation: Institute of Neurobiology, University Münster, Münster, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Klämbt
authors.affiliation: Institute of Neuropathology, University Hospital Münster, Pottkamp 2, 48129, Münster, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Paulus
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D030801:Animals, Genetically Modified; D005075:Biological Evolution; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics; D005910:Glioma / Q000473:pathology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D015398:Signal Transduction; D060245:Tetraspanin 29 / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D060245:Tetraspanin 29; D049452:Green Fluorescent Proteins; D017479:Receptors, Platelet-Derived Growth Factor
keywords: CD9; Drosophila; Glioma; PDGFR; tsp2A