Involvement of CD9 and PDGFR in migration is evolutionarily conserved from Drosophila glia to human glioma
Involvement of CD9 and PDGFR in migration is evolutionarily conserved from Drosophila glia to human glioma
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DOI：
10.1007/s11060-015-1864-4
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发表时间：
2015-09-01
影响因子：
3.9
通讯作者：
Paulus, Werner
中科院分区：
文献类型：
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作者：
Jeibmann, Astrid;Halama, Kathrin;Paulus, Werner
血小板衍生生长因子受体(PDGFR)信号转导通路在恶性胶质瘤的生物学过程中发挥着重要作用。为了研究PDGFR信号在胶质瘤形成中的调控机制，我们采用了果蝇胶质瘤模型和遗传筛选来寻找与PDGFR的果蝇同源物PVR相互作用的基因。组成性激活的PVR(Lambda PVR)的胶质细胞表达导致幼虫后期胶质细胞过度迁移和致死。在与测试菌株杂交的3316个dsRNA菌株中，有128个基因将致死性转移到蛹期，其中包括Tetraspanin 2A(Tsp2A)。在第二步中，研究了所有果蝇Tetraspanins的基因敲除。在所有的Tetraspanin dsRNA菌株中，只有TSP2A的敲除部分挽救了PVR诱导的表型。人CD9(TSPAN29/MRP-1)是TSP2A的同源物，在胶质瘤细胞系A172和U343 MG以及大多数胶质母细胞瘤标本中均有表达(16/22，73%)。此外，原位邻近连接实验显示CD9与PDGFRα和β密切相关。在U343 MG细胞中，CD9基因敲除可阻断PDGF-BB刺激迁移。综上所述，从果蝇到人脑胶质瘤，CD9对PDGFR信号的调控在进化上是保守的，并在胶质细胞的迁移中发挥作用。
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.