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首页> 外文期刊>Brain Tumor Pathology >Persistent roles of signal transduction of platelet-derived growth factor B in genesis, growth, and anaplastic transformation of gliomas in an in-vivo serial transplantation model
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Persistent roles of signal transduction of platelet-derived growth factor B in genesis, growth, and anaplastic transformation of gliomas in an in-vivo serial transplantation model

机译：体内串行移植模型中血小板衍生生长因子B信号转导在神经胶质瘤的发生，生长和间变性转化中的持久作用

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We previously reported that retrovirally transduced platelet-derived growth factor-B (PDGFB) in glial progenitors of the rat cerebral white matter, subventricular zone, or brain stem induced malignant brain tumors closely resembling human glioblastoma (GBM). While human GBMs may progress over the period of several months to a few years, prospective, long-term in-vivo observation of histological changes of the tumor tissues is not feasible in these models, because the animals undergo rapid tumor progression and mortality within approximately 1 month. We thus performed successive, long-term in-vivo transplantation of the PDGFB-induced tumor cells into the rat cerebrum. Primary retroviral transduction of PDGFB in the glial progenitors of the rat basal ganglia induced malignant glioma resembling human GBM or anaplastic oligodendroglioma (AOL) consisting of relatively monomorphous tumor cells expressing markers for the oligodendrocyte lineage. In the course of long-term successive transplantation, tumor cells presented pleomorphism as well as focal GFAP expression. This suggests that secondary chromosomal aberration and dysregulation of gene expression following accelerated cell cycle by PDGFB stimulation would induce morphological and immunophenotypic changes in tumor cells. Furthermore, while the primary tumors contained only a minor fraction of proviral GFP-expressing or hemagglutinin-expressing cells, most tumor cells came to express these proviral genes in the course of serial transplantation suggesting a persistent role of PDGFB-expressing cells in maintenance and growth of the tumors. This model would be useful for investigation of the long-term effects of PDGFB stimulation in glioma tissues on anaplastic evolution.
机译：我们先前曾报道过，大鼠脑白质，脑室下区或脑干的神经胶质祖细胞中逆转录病毒转导的血小板衍生生长因子B（PDGFB）诱导的恶性脑肿瘤与人胶质母细胞瘤（GBM）极为相似。尽管人类GBM可能会在数月至数年的时间内发展，但在这些模型中无法对肿瘤组织的组织学变化进行前瞻性，长期的体内观察，因为动物会在大约10个月内经历快速的肿瘤进展和死亡。 1个月。因此，我们进行了PDGFB诱导的肿瘤细胞连续，长期的体内移植到大鼠大脑中。 PDGFB在大鼠基底神经节的神经胶质祖细胞中的初级逆转录病毒转导诱导恶性神经胶质瘤，类似于人GBM或间变性少突胶质神经胶质瘤（AOL），由表达少突胶质细胞谱系标记的相对单态性肿瘤细胞组成。在长期连续移植过程中，肿瘤细胞呈现多态性和局灶性GFAP表达。这表明PDGFB刺激加速细胞周期后，继发性染色体畸变和基因表达失调将诱导肿瘤细胞的形态学和免疫表型改变。此外，尽管原发性肿瘤仅包含一小部分表达前GFP的细胞或表达血凝素的细胞，但大多数肿瘤细胞在连续移植过程中表达了这些前病毒基因，提示PDGFB表达的细胞在维持和生长中具有持久作用。的肿瘤。该模型可用于研究PDGFB刺激在胶质瘤组织中对间变性进化的长期影响。

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