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首页> 外文期刊>Glia >PDGF stimulates the massive expansion of glial progenitors in the neonatal forebrain
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PDGF stimulates the massive expansion of glial progenitors in the neonatal forebrain

机译：PDGF刺激新生前脑中神经胶质祖细胞的大量扩张

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Platelet-derived growth factor (PDGF) plays a major role in regulating migration, proliferation, and differentiation of glial progenitors during normal brain development and in the abnormal proliferation and dispersion that drives the formation of malignant gliomas. To further explore the relationship between PDGF's effects on normal glial progenitors and its role in the formation of gliomas, we infected progenitor cells in the subventricular zone (SVZ) of the lateral ventricle of neonatal rat pups with a retrovirus that expresses PDGF and green fluorescent protein (GFP). At 3 days post-injection (dpi), a proliferation of PDGFRα+ progenitors was seen in the SVZ and white matter around the injection site and by 10 dpi the animals had large diffusely infiltrating tumors that resembled glioblastomas. The tumors contained a massive proliferation of both infected and uninfected PDGFRα+ progenitors, suggesting that PDGF was driving tumor formation via both autocrine and paracrine signaling. Rats co-injected with two retroviruses (one that expresses PDGF-IRES-DSRED and one that expresses only GFP) formed tumors that contained a mixture of DSRED+ cells (PDGF producers) and GFP+ cells (recruited progenitors). Time-lapse microscopy of slice cultures confirmed that both DSRED+ and GFP+ cells were highly migratory and proliferative. Furthermore, adding exogenous PDGF to slice cultures generated from nontumorbearing brains (injected with control GFP retrovirus only) stimulated the migration and proliferation of GFP+ progenitors. These findings reveal the inherent growth factor responsiveness and tumorigenic potential of PDGFRα+ progenitors and highlight the importance of paracrine signaling in stimulating glioma growth and infiltration.
机译：血小板源性生长因子（PDGF）在正常脑发育过程中以及在胶质祖细胞的迁移，增殖和分化以及驱动恶性神经胶质瘤形成的异常增殖和分散中起着重要作用。为了进一步探讨PDGF对正常神经胶质祖细胞的作用及其在神经胶质瘤形成中的作用之间的关系，我们用表达PDGF和绿色荧光蛋白的逆转录病毒感染了新生大鼠幼鼠侧脑室下室区（SVZ）的祖细胞（GFP）。注射后第3天（dpi），在注射部位周围的SVZ和白质中观察到PDGFRα+祖细胞的增殖，到10 dpi时，动物出现了类似于胶质母细胞瘤的大型弥漫性浸润性肿瘤。肿瘤包含感染和未感染的PDGFRα+祖细胞的大量增殖，表明PDGF通过自分泌和旁分泌信号传导来驱动肿瘤形成。共注射两种逆转录病毒（一种表达PDGF-IRES-DSRED，另一种仅表达GFP）的大鼠形成了肿瘤，其中含有DSRED +细胞（PDGF产生者）和GFP +细胞（募集的祖细胞）的混合物。切片培养物的延时显微镜证实，DSRED +和GFP +细胞均高度迁移和增殖。此外，将外源PDGF添加到由非肿瘤脑（仅注射对照GFP逆转录病毒）产生的切片培养物中可刺激GFP +祖细胞的迁移和增殖。这些发现揭示了PDGFRα+祖细胞固有的生长因子反应性和致瘤潜力，并突出了旁分泌信号在刺激神经胶质瘤生长和浸润中的重要性。

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