Comprehensive characterization of neuroblastoma cell line subtypes reveals bilineage potential similar to neural crest stem cells.
Comprehensive characterization of neuroblastoma cell line subtypes reveals bilineage potential similar to neural crest stem cells.
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DOI：
10.1186/1471-213x-9-12
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发表时间：
2009-02-12
影响因子：
--
通讯作者：
Mora J
中科院分区：
文献类型：
--
作者：
Acosta S;Lavarino C;Paris R;Garcia I;de Torres C;Rodríguez E;Beleta H;Mora J
神经母细胞瘤（NBT）来源于神经嵴干细胞（NCSC）。组织学上，NBT由神经母细胞和许旺细胞组成。在培养中，神经母细胞（N-），基质粘附（S-）和中间表型（I-）细胞亚型自发产生。在此，根据胚胎周围神经系统发育标志物（GAP 43、Phox 2b、Sox 10、c-kit、GD 2、NF 68、波形蛋白、S100β、钙周期蛋白和ABCG 2）、形态学特征、基因表达和分化潜能来表征神经母细胞瘤（NB）细胞系亚型。I型细胞作为一个双能（神经元和神经胶质）分化阶段进行了研究。在所有NB亚型中观察到NCSC（GAP 43、c-kit、NF 68、vimentin和Phox 2b）和未分化细胞（ABCG 2）标记物的阳性免疫染色。N型和I型细胞显示胞质膜GD 2染色，而核钙周期蛋白仅限于S型。N型和I型细胞表现出相似的表型和免疫反应模式。差异基因表达与每个细胞亚型相关。N-和I-型细胞表现出类似的分化能力，对神经元和神经胶质细胞系的命运。S型细胞，诱导后，没有显示出神经元样表型，尽管基因表达的变化。结果表明，N型和I型NB细胞亚型代表一个不成熟的双系阶段，能够向神经元和神经胶质的命运诱导分化后的进展。S型细胞似乎不可逆地致力于神经胶质细胞系的命运。
Neuroblastic tumors (NBT) derive from neural crest stem cells (NCSC). Histologically, NBT are composed by neuroblasts and Schwannian cells. In culture, neuroblastic (N-), substrate-adherent (S-) and intermediate phenotype (I-) cell subtypes arise spontaneously. Here, neuroblastoma (NB) cell line subtypes were characterized according to embryonic peripheral nervous system development markers (GAP43, Phox2b, Sox10, c-kit, GD2, NF68, vimentin, S100β, calcyclin and ABCG2), morphological features, gene expression and differentiation potential. I-type cells were investigated as a bipotential (neuronal and glial) differentiation stage. Positive immunostaining of NCSC (GAP43, c-kit, NF68, vimentin and Phox2b) and undifferentiated cell (ABCG2) markers was observed in all NB subtypes. N- and I-type cells displayed cytoplasmic membrane GD2 staining, while nuclear calcyclin was restricted to S-type. N- and I-type cells showed similar phenotype and immunoreactivity pattern. Differential gene expression was associated with each cell subtype. N- and I-type cells displayed similar differentiation capacity towards neuronal and glial lineage fates. S-type cells, upon induction, did not show a neuronal-like phenotype, despite gene expression changes. Results suggest that N- and I-type NB cell subtypes represent an immature bilineage stage, able to progress towards neuronal and glial fates upon induction of differentiation. S-type cells appear irreversibly committed to a glial lineage fate.