Involvement of CD9 and PDGFR in migration is evolutionarily conserved from Drosophila glia to human glioma
2015 (English)In: Journal of Neuro-Oncology, ISSN 0167-594X, E-ISSN 1573-7373, Vol. 124, no 3, 373-383 p.Article in journal (Refereed) Published
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 (lambda Pvr) 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 alpha and beta. 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.
Place, publisher, year, edition, pages
2015. Vol. 124, no 3, 373-383 p.
Drosophila, Glioma, CD9, tsp2A, PDGFR
Cell and Molecular Biology
IdentifiersURN: urn:nbn:se:uu:diva-265927DOI: 10.1007/s11060-015-1864-4ISI: 000361902000005PubMedID: 26224160OAI: oai:DiVA.org:uu-265927DiVA: diva2:866975
FunderGerman Research Foundation (DFG), PA328/7-1German Research Foundation (DFG), Ko-4345/1-1