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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Cancerous stem cells can arise from pediatric brain tumors
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Cancerous stem cells can arise from pediatric brain tumors

机译：小儿脑肿瘤可引起癌性干细胞

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Pediatric brain tumors are significant causes of morbidity and mortality. It has been hypothesized that they derive from self-renewing multipotent neural stem cells. Here, we tested whether different pediatric brain tumors, including medulloblastomas and gliomas, contain cells with properties similar to neural stem cells. We find that tumor-derived progenitors form neurospheres that can be passaged at clonal density and are able to self-renew. Under conditions promoting differentiation, individual cells are multipotent, giving rise to both neurons and glia, in proportions that reflect the tumor of origin. Unlike normal neural stem cells, however, tumor-derived progenitors have an unusual capacity to proliferate and sometimes differentiate into abnormal cells with multiple differentiation markers. Gene expression analysis reveals that both whole tumors and tumor-derived neurospheres express many genes characteristic of neural and other stem cells, including CD133, Sox2, musashi-11 bmi-1, maternal embryonic leucine zipper kinase, and phosphoserine phosphatase, with variation from tumor to tumor. After grafting to neonatal rat brains, tumor-derived neurosphere cells migrate, produce neurons and glia, and continue to proliferate for more than 4 weeks. The results show that pediatric brain tumors contain neural stem-like cells with altered characteristics that may contribute to tumorigenesis. This finding may have important implications for treatment by means of specific targeting of stem-like cells within brain tumors.
机译：小儿脑肿瘤是发病率和死亡率的重要原因。假设它们源自自我更新的多能神经干细胞。在这里，我们测试了包括髓母细胞瘤和神经胶质瘤在内的各种儿科脑肿瘤是否含有与神经干细胞性质相似的细胞。我们发现肿瘤来源的祖细胞形成神经球，可以在克隆密度下传代并且能够自我更新。在促进分化的条件下，单个细胞是多能的，以反映起源肿瘤的比例产生神经元和神经胶质。但是，与正常的神经干细胞不同，肿瘤来源的祖细胞具有异常的增殖能力，有时具有多种分化标记物，可以分化为异常细胞。基因表达分析表明，整个肿瘤和肿瘤来源的神经球都表达神经和其他干细胞的许多基因，包括CD133，Sox2，Musashi-11 bmi-1，母体胚胎亮氨酸拉链激酶和磷酸丝氨酸磷酸酶，但与肿瘤不同对肿瘤。移植到新生大鼠大脑后，肿瘤来源的神经球细胞迁移，产生神经元和神经胶质，并持续增殖超过4周。结果表明，小儿脑肿瘤含有神经干样细胞，其特征发生改变，可能有助于肿瘤发生。这一发现可能对脑肿瘤内干细胞的特异性靶向治疗具有重要意义。

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