RRC ID 34867
Author Jeibmann A, Halama K, Witte HT, Kim SN, Eikmeier K, Koos B, Klämbt C, Paulus W.
Title Involvement of CD9 and PDGFR in migration is evolutionarily conserved from Drosophila glia to human glioma.
Journal J. Neurooncol.
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.
Volume 124(3)
Pages 373-83
Published 2015-9
DOI 10.1007/s11060-015-1864-4
PII 10.1007/s11060-015-1864-4
PMID 26224160
MeSH Analysis of Variance Animals Animals, Genetically Modified Biological Evolution Brain Neoplasms / genetics Brain Neoplasms / pathology Cell Line, Tumor Cell Movement / drug effects Cell Movement / genetics Cell Movement / physiology* Cell Survival / drug effects Cell Survival / genetics Dose-Response Relationship, Drug Drosophila Drosophila Proteins / genetics Glioma / pathology* Green Fluorescent Proteins / genetics Green Fluorescent Proteins / metabolism Humans Neuroglia / metabolism* Neuroglia / pathology RNA, Messenger / metabolism RNA, Small Interfering / pharmacology Receptors, Platelet-Derived Growth Factor / metabolism* Receptors, Platelet-Derived Growth Factor / pharmacology Signal Transduction Tetraspanin-29 / metabolism*
IF 3.06
Times Cited 0
WOS Category CLINICAL NEUROLOGY ONCOLOGY
Resource
Drosophila 11415R-2 10741R-3 9093R-3 9494R-1 9494R-2 4591R-1 4591R-2