Human Medulloblastoma Cell Lines: Investigating on Cancer Stem Cell-Like Phenotype
Human Medulloblastoma Cell Lines: Investigating on Cancer Stem Cell-Like Phenotype
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DOI：
10.3390/cancers12010226
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发表时间：
2020-01-01
期刊：
影响因子：
5.2
通讯作者：
Mancuso, Mariateresa
中科院分区：
文献类型：
--
作者：
Casciati, Arianna;Tanori, Mirella;Mancuso, Mariateresa
髓母细胞瘤（MB）是最常见的儿童恶性脑肿瘤。尽管新的治疗方法取得了进展，但复发、发病和死亡的风险仍然很大，对幸存者的长期不良影响也很大。由于其自我更新能力和多谱系分化潜力，癌症干细胞样细胞（CSC）的分数对于肿瘤的起始、生长和对治疗的抗性至关重要。为了开发新的CSC靶向疗法，需要使用富集和稳定的MB-CSC群体进行进一步深入的研究。这项工作旨在鉴定三种可用的人类细胞系（DAOY，D341和D283）中CSC的量，描述了基于干细胞标记物表达的不同方法。首先，我们探讨了特定干细胞标志物的基因和蛋白质表达模式的潜在差异。然后，为了识别和区分未分化细胞和分化细胞，使用基于高频介电电泳方法的物理表征方法对MB细胞进行表征。最后，我们比较了它们在裸鼠体内的致瘤潜力。一致地，我们的发现将D283人细胞系鉴定为CSC的理想模型，为使用商业人MB细胞系开发新的战略CSC靶向疗法提供了重要证据。
Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Despite the progress of new treatments, the risk of recurrence, morbidity, and death remains significant and the long-term adverse effects in survivors are substantial. The fraction of cancer stem-like cells (CSCs) because of their self-renewal ability and multi-lineage differentiation potential is critical for tumor initiation, growth, and resistance to therapies. For the development of new CSC-targeted therapies, further in-depth studies are needed using enriched and stable MB-CSCs populations. This work, aimed at identifying the amount of CSCs in three available human cell lines (DAOY, D341, and D283), describes different approaches based on the expression of stemness markers. First, we explored potential differences in gene and protein expression patterns of specific stem cell markers. Then, in order to identify and discriminate undifferentiated from differentiated cells, MB cells were characterized using a physical characterization method based on a high-frequency dielectrophoresis approach. Finally, we compared their tumorigenic potential in vivo, through engrafting in nude mice. Concordantly, our findings identified the D283 human cell line as an ideal model of CSCs, providing important evidence on the use of a commercial human MB cell line for the development of new strategic CSC-targeting therapies.