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: Astrid Jeibmann, Kathrin Halama, Hanna Theresa Witte, Su Na Kim, Kristin Eikmeier, Björn Koos, Christian Klämbt, Werner Paulus
• Journal: Journal of neuro-oncology (J Neurooncol) Vol. 124 Issue 3 Pg. 373-83 (Sep 2015) ISSN: 1573-7373 [Electronic] United States
• PMID: 26224160 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Drosophila Proteins
• RNA, Messenger
• RNA, Small Interfering
• Tetraspanin 29
• Green Fluorescent Proteins
• Receptors, Platelet-Derived Growth Factor

Topics

• Analysis of Variance
• Animals
• Animals, Genetically Modified
• Biological Evolution
• Brain Neoplasms (genetics, pathology)
• Cell Line, Tumor
• Cell Movement (drug effects, genetics, physiology)
• Cell Survival (drug effects, genetics)
• Dose-Response Relationship, Drug
• Drosophila
• Drosophila Proteins (genetics)
• Glioma (pathology)
• Green Fluorescent Proteins (genetics, metabolism)
• Humans
• Neuroglia (metabolism, pathology)
• RNA, Messenger (metabolism)
• RNA, Small Interfering (pharmacology)
• Receptors, Platelet-Derived Growth Factor (metabolism, pharmacology)
• Signal Transduction
• Tetraspanin 29 (metabolism)