Gliosarcoma stem cells undergo glial and mesenchymal differentiation in vivo.
Gliosarcoma stem cells undergo glial and mesenchymal differentiation in vivo.
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DOI：
10.1002/stem.264
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发表时间：
2010-02
期刊：
影响因子：
5.2
通讯作者：
Mikkelsen, Tom
中科院分区：
文献类型：
--
作者：
DeCarvalho, Ana C.;Nelson, Kevin;Lemke, Nancy;Lehman, Norman L.;Arbab, Ali S.;Kalkanis, Steven;Mikkelsen, Tom
癌症干细胞（CSC）的特征在于其自我更新潜力，以及其在原位异种移植物中分化和表型复制原始肿瘤的能力。胶质母细胞瘤（GBM）细胞在含有血清的培养基中的长期增殖导致CSC的损失以及在遗传上和生物学上与亲本肿瘤不同的细胞的生长。相比之下，使用神经球测定，用于选择和增殖CNS衍生干细胞的无血清培养物，允许选择含有CSC的亚群。胶质肉瘤（GS），一种形态学变体，包含约2%的GBM，呈现双相生长模式，由胶质和化生间充质成分组成。为了评估神经球测定是否允许扩增具有“胶质肉瘤干细胞”性质的细胞亚群，能够繁殖这种恶性肿瘤的两种组分，我们从原发性GS和GBM手术标本中产生了神经球和血清培养物。GBM和GS样本的神经球培养物表达神经干细胞标记物Sox 2、Msi 1和Nestin。与GBM神经球系相反，GS神经球对干细胞标志物CD 133呈阴性。所有的神经球细胞系都产生了高级别的侵袭性原位肿瘤异种移植物，其组织学特征与亲本肿瘤非常相似，表明这些培养物确实富含CSC。值得注意的是，低传代GS血清培养物保留了干细胞标志物的表达、形成神经球的能力和致瘤性。GS实验肿瘤表型模仿亲本肿瘤，表现出双相胶质和间充质成分，构成了临床相关的模型，以研究GBM间充质分化。
Cancer stem cells (CSCs) are characterized by their self-renewing potential, and by their ability to differentiate and phenocopy the original tumor in orthotopic xenografts. Long term propagation of glioblastoma (GBM) cells in serum containing medium results in loss of the CSCs and outgrowth of cells genetically and biologically divergent from the parental tumors. In contrast, the use of neurosphere assay, a serum-free culture for selection and propagation of CNS-derived stem cells, allows the selection of a subpopulation containing CSCs. Gliosarcoma (GS), a morphological variant comprising approximately 2% of GBMs, present a biphasic growth pattern, composed of glial and metaplastic mesenchymal components. To assess whether the neurosphere assay would allow the amplification of a subpopulation of cells with “gliosarcoma stem cell” properties, capable of propagating both components of this malignancy, we have generated neurospheres and serum cultures from primary GS and GBM surgical specimens. Neurosphere cultures from GBM and GS samples expressed neural stem cell markers Sox2, Msi1 and Nestin. In contrast to the GBM neurosphere lines, the GS neurospheres were negative for the stem cell marker CD133. All neurosphere lines generated high grade invasive orthotopic tumor xenografts, with histological features strickingly similar to the parental tumors, demonstrating that these cultures indeed are enriched in CSCs. Remarkably, low passage GS serum culture retained the expression of stem cell markers, the ability to form neurospheres, and tumorigenicity. The GS experimental tumors phenocopied the parental tumor, exhibiting biphasic glial and mesenchymal components, constituting a clinically relevant model to investigate mesenchymal differentiation in GBMs.
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影响因子：
3.7
作者：
Actor, B;Cobbers, JMJL;Weber, RG
通讯作者：
Weber, RG
DOI：
10.1097/00005072-199609000-00004
发表时间：
1996-09-01
影响因子：
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作者：
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作者：
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影响因子：
11.2
作者：
Galli, R;Binda, E;Vescovi, A
通讯作者：
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