Glioblastoma-derived stem cell-enriched cultures form distinct subgroups according to molecular and phenotypic criteria
Glioblastoma-derived stem cell-enriched cultures form distinct subgroups according to molecular and phenotypic criteria
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DOI：
10.1038/sj.onc.1210949
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发表时间：
2008-05-01
期刊：
影响因子：
8
通讯作者：
Lamszus, K.
中科院分区：
文献类型：
--
作者：
Guenther, H. S.;Schmidt, N. O.;Lamszus, K.
具有干细胞样特性的肿瘤细胞可以通过使用选择用于神经干细胞扩增的条件从人胶质母细胞瘤中培养。我们从胶质母细胞瘤标本中产生细胞系，目的是获得胶质瘤干细胞生物学的模型系统。在神经干细胞条件下建立的九个细胞系的表达谱的无监督分析产生了两个不同的集群。四个细胞系的特点是神经发育基因的表达。它们表现出沿着神经元、星形胶质细胞和少突胶质细胞谱系的多能分化特征，在体外球形生长，表达CD 133，并在体内形成高度侵袭性肿瘤。其他5个细胞系共享表达特征，富含细胞外基质相关基因，具有更有限的分化能力，不含或含有更少的CD 133（+）细胞，体外半贴壁或贴壁生长，体内致瘤性和侵袭性降低。我们的研究结果表明，具有完整干细胞样表型的稳定的多能胶质母细胞瘤细胞系表达神经发育基因作为一个独特的特征，这可能提供治疗靶向的机会。产生另一个不同的细胞系簇，显示类似的同质性蛋白。干细胞微小但有限的特性表明存在不同的表型，每种表型都可能导致胶质母细胞瘤的典型表现。
Tumor cells with stem cell-like properties can be cultured from human glioblastomas by using conditions that select for the expansion of neural stem cells. We generated cell lines from glioblastoma specimens with the goal to obtain model systems for glioma stem cell biology. Unsupervised analysis of the expression profiles of nine cell lines established under neural stem cell conditions yielded two distinct clusters. Four cell lines were characterized by the expression of neurodevelopmental genes. They showed a multipotent differentiation profile along neuronal, astroglial and oligodendroglial lineages, grew spherically in vitro, expressed CD133 and formed highly invasive tumors in vivo. The other five cell lines shared expression signatures enriched for extracellular matrix-related genes, had a more restricted differentiation capacity, contained no or fewer CD133(+) cells, grew semiadherent or adherent in vitro and displayed reduced tumorigenicity and invasion in vivo. Our findings show that stable, multipotent glioblastoma cell lines with a full stem-like phenotype express neurodevelopmental genes as a distinctive feature, which may offer therapeutic targeting opportunities. The generation of another distinct cluster of cell lines showing similarly homogeneous pro. ling but restricted stem cell properties suggests that different phenotypes exist, each of which may lead to the typical appearance of glioblastoma.