| 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 |
2015-9-1
|
| 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 |
3.267
|
| Times Cited |
6
|
|
WOS Category
|
CLINICAL NEUROLOGY
ONCOLOGY
|
| Resource |
| Drosophila |
11415R-2
10741R-3
9093R-3
9494R-1
9494R-2
4591R-1
4591R-2 |
