Neural Precursor-Derived Pleiotrophin Mediates Subventricular Zone Invasion by Glioma.
Neural Precursor-Derived Pleiotrophin Mediates Subventricular Zone Invasion by Glioma.
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DOI：
10.1016/j.cell.2017.07.016
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发表时间：
2017-08-24
期刊：
影响因子：
64.5
通讯作者：
Monje M
中科院分区：
文献类型：
--
作者：
Qin EY;Cooper DD;Abbott KL;Lennon J;Nagaraja S;Mackay A;Jones C;Vogel H;Jackson PK;Monje M
侧脑室脑室下区（SVZ）是儿童和成人胶质瘤扩散的常见和重要部位，但对其介导的细胞和分子机制知之甚少。我们证明，神经前体细胞（NPC）：胶质瘤细胞通信的基础上，这种倾向的胶质瘤通过分泌的化学引诱物信号向胶质瘤细胞的家定殖SVZ。SVZ NPC分泌因子的生物化学、蛋白质组学和功能分析揭示了神经突生长促进因子多效生长因子，沿着所需的结合伙伴SPARCL/SPARCL 1和HSP 90 B，作为这种化学引诱物效应的关键介质。多效生长因子表达在SVZ中强烈富集，并且多效生长因子敲低显著降低了鼠脑中SVZ的胶质瘤侵袭。多效营养因子与结合伴侣复合，激活胶质瘤Rho/ROCK信号传导，并且ROCK抑制降低了对SVZ NPC分泌因子的侵袭。这些发现表明NPC的致病作用：胶质瘤的相互作用和潜在的治疗靶点，以限制胶质瘤的侵袭。神经前体细胞衍生的多效生长因子所产生的趋化作用是高级别胶质瘤侵袭侧脑室室下区的偏好的基础，为针对胶质瘤侵袭的治疗开发提供了潜在的靶点。
The lateral ventricle subventricular zone (SVZ) is a frequent and consequential site of pediatric and adult glioma spread, but the cellular and molecular mechanisms mediating this are poorly understood. We demonstrate that neural precursor cell (NPC):glioma cell communication underpins this propensity of glioma to colonize the SVZ through secretion of chemoattractant signals toward which glioma cells home. Biochemical, proteomic, and functional analyses of SVZ NPC-secreted factors revealed the neurite outgrowth-promoting factor pleiotrophin, along with required binding partners SPARC/SPARCL1 and HSP90B, as key mediators of this chemoattractant effect. Pleiotrophin expression is strongly enriched in the SVZ, and pleiotrophin knockdown starkly reduced glioma invasion of the SVZ in the murine brain. Pleiotrophin, in complex with the binding partners, activated glioma Rho/ROCK signaling, and ROCK inhibition decreased invasion toward SVZ NPC-secreted factors. These findings demonstrate a pathogenic role for NPC:glioma interactions and potential therapeutic targets to limit glioma invasion. The chemoattractant effect exerted by neural precursor cell-derived pleiotrophin underlies the preference of high-grade glioma to invade the lateral ventricle subventricular zone, providing potential targets for therapeutic development against glioma invasion.
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影响因子：
64.5
作者：
Brose, K;Bland, KS;Kidd, T
通讯作者：
Kidd, T
影响因子：
3.7
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作者：
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