PDGF-B induces a homogeneous class of oligodendrogliomas from embryonic neural progenitors
PDGF-B induces a homogeneous class of oligodendrogliomas from embryonic neural progenitors
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DOI：
10.1002/ijc.24206
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发表时间：
2009-05-15
影响因子：
6.4
通讯作者：
Malatesta, Paolo
中科院分区：
文献类型：
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作者：
Appolloni, Irene;Calzolari, Filippo;Malatesta, Paolo
我们描述了在胚胎神经前体细胞中过表达PDGF-B后发生的小鼠胶质瘤。我们的组织病理学、免疫组织化学和全基因组表达分析显示，PDGF-B诱导的肿瘤之间有惊人的一致性，尽管它们是通过转导高度异质的前体细胞群产生的，这些前体细胞以其产生中枢神经系统的所有细胞类型的能力而闻名。将我们的微阵列数据与已公布的许多不同类型小鼠神经细胞的基因表达数据集进行比较，发现我们的肿瘤细胞和少突胶质前体细胞之间的相关性最密切，从而明确证实PDGF-B诱导的胶质瘤是纯粹的少突胶质细胞瘤。重要的是，我们表明这种一致性可能是由于PDGF-B的过度表达能够将有能力的胚胎神经前体重新指定为少突胶质细胞系，提供了PDGF-B的转化活性受到靶细胞发育潜力影响的证据。有趣的是，我们发现PDGF-B诱导的肿瘤具有不同的增殖细胞群。然而，只有PDGF-B过表达的细胞是致癌的，这表明来自肿瘤的旁分泌信号无法转化旁观者细胞。(C)2008年Wiley-Liss，Inc.
We describe the generation of mouse gliomas following the overexpression of PDGF-B in embryonic neural progenitors. Our histopathological, immunohistochemical and genome-wide expression analyses revealed a surprising uniformity among PDGF-B induced tumors, despite they were generated by transducing a highly heterogeneous population of progenitor cells known for their ability to produce all the cell types of the central nervous system. Comparison of our microarray data with published gene expression data sets for many different murine neural cell types revealed a closest correlation between our tumor cells and oligodendrocyte progenitor cells, confirming definitively that PDGF-B-induced gliomas are pure oligodendrogliomas. Importantly, we show that this uniformity is likely due to the ability of PDGF-B overexpression to respecify competent embryonic neural precursors toward the oligodendroglial lineage, providing evidence that the transforming activity of PDGF-B is influenced by the developmental potential of the targeted cells. Interestingly, we found that PDGF-B-induced tumors harbor different proliferating cell populations. However only PDGF-B-overexpressing cells are tumorigenic, indicating that paracrine signaling from the tumor is unable to transform bystander cells. (C) 2008 Wiley-Liss, Inc.