Heterogeneous phenotype of human glioblastoma: In vitro study
Heterogeneous phenotype of human glioblastoma: In vitro study
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DOI：
10.1002/cbf.2988
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发表时间：
2014-03-01
影响因子：
3.6
通讯作者：
Melcarne, Antonio
中科院分区：
文献类型：
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作者：
Denysenko, Tetyana;Gennero, Luisa;Melcarne, Antonio
胶质母细胞瘤是最致命的原发脑肿瘤。越来越多的证据表明，脑瘤中含有干细胞，即所谓的癌症干细胞(CSCs)。干细胞标记物CD133被报道用于鉴定GBM中的CSC群体。进一步的研究表明，CD133阴性细胞具有相似的特性，能够启动肿瘤、自我更新和进行多系分化。基底细胞瘤是一种高度异质性的肿瘤，可能包含不同的干细胞群，具有不同的功能特性。我们从手术标本中建立了五个GBM细胞系，根据标志物的表达、增殖和分化潜能对其进行了鉴定。CD133阳性细胞系在神经球条件下表现出较高的增殖率，并具有明显的向神经元分化的潜能。而CD133低表达的两株细胞在体外具有间充质特性，即血清条件下的高增殖率和间充质细胞类型的分化。此外，我们还比较了羟基脲处理的GBM细胞株的耐药能力。我们的结果表明，CSC的概念比以前认为的更复杂，CD133不能定义GBM内的整个干细胞群体。至少存在两种不同的GBM CSCs亚型，它们可能具有不同的生物学特性，暗示着不同的治疗策略。版权所有(C)2013 John Wiley&Sons，Ltd.
Glioblastomas (GBMs) are the most lethal primary brain tumours. Increasing evidence shows that brain tumours contain the population of stem cells, so-called cancer stem cells (CSCs). Stem cell marker CD133 was reported to identify CSC population in GBM. Further studies have indicated that CD133 negative cells exhibiting similar properties and are able to initiate the tumour, self-renew and undergo multilineage differentiation. GBM is a highly heterogeneous tumour and may contain different stem cell populations with different functional properties. We characterized five GBM cell lines, established from surgical samples, according to the marker expression, proliferation and differentiation potential. CD133 positive cell lines showed increased proliferation rate in neurosphere condition and marked differentiation potential towards neuronal lineages. Whereas two cell lines low-expressing CD133 marker showed mesenchymal properties in vitro, that is high proliferation rate in serum condition and differentiation in mesenchymal cell types. Further, we compared therapy resistance capacity of GBM cell lines treated with hydroxyurea. Our results suggest that CSC concept is more complex than it was believed before, and CD133 could not define entire stem cell population within GBM. At least two different subtypes of GBM CSCs exist, which may have different biological characteristics and imply different therapeutic strategies. Copyright (c) 2013 John Wiley & Sons, Ltd.