Clinical relevance of tumor cells with stem-like properties in pediatric brain tumors.
Clinical relevance of tumor cells with stem-like properties in pediatric brain tumors.
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DOI：
10.1371/journal.pone.0016375
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发表时间：
2011-01-28
期刊：
影响因子：
3.7
通讯作者：
Junier MP
中科院分区：
文献类型：
--
作者：
Thirant C;Bessette B;Varlet P;Puget S;Cadusseau J;Tavares Sdos R;Studler JM;Silvestre DC;Susini A;Villa C;Miquel C;Bogeas A;Surena AL;Dias-Morais A;Léonard N;Pflumio F;Bièche I;Boussin FD;Sainte-Rose C;Grill J;Daumas-Duport C;Chneiweiss H;Junier MP
原始脑肿瘤是儿童癌症相关死亡的主要原因。具有干细胞样特性的肿瘤细胞（TSCs）被认为是肿瘤发生和治疗抗性的原因，已从成人的高级别胶质瘤中分离出来。肿瘤干细胞是否是儿童脑肿瘤的常见组成部分，是否具有临床意义仍有待确定。采用细胞生物学技术从55例儿童脑肿瘤样本中分离出具有自我更新特性的肿瘤细胞，无论其组织病理学和恶性程度如何（57%的胚胎性肿瘤，57%的低级别胶质瘤和神经胶质瘤，70%的室管膜瘤，91%的高级别胶质瘤）。大多数高级别胶质瘤源性六钩蚴（10/12）持续长期自我更新，类似于神经干细胞（>7自我更新），而具有有限更新能力的细胞类似于神经祖细胞在所有其他肿瘤中占主导地位。无论肿瘤实体如何，年轻年龄组与类似于神经干细胞的自我更新特性相关（P = 0.05，卡方检验）。 队列的存活分析显示具有长期自我更新能力的细胞的分离与更高的患者死亡率之间的关联（P = 0.013，对数秩检验）。 低级别和高级别神经胶质瘤培养物的取样显示，形成六钩蚴的自我更新细胞共享包括胚胎和神经干细胞标记物的分子谱。对高级别胶质瘤和一个低级别胶质瘤培养物的亚组进行的进一步表征显示了该特征与间充质标志物、细胞的放射化学抗性和脑内移植后侵袭性肿瘤的形成的组合。在影响成人患者的脑肿瘤中，仅从高级别胶质瘤中分离出TSC。相比之下，我们的数据显示，具有干细胞样或祖细胞样特性的肿瘤细胞可以从广泛的组织学亚型和儿科脑肿瘤等级中分离出来。他们认为，促进肿瘤发展的细胞机制在成人和儿童脑肿瘤之间存在差异。
Primitive brain tumors are the leading cause of cancer-related death in children. Tumor cells with stem-like properties (TSCs), thought to account for tumorigenesis and therapeutic resistance, have been isolated from high-grade gliomas in adults. Whether TSCs are a common component of pediatric brain tumors and are of clinical relevance remains to be determined. Tumor cells with self-renewal properties were isolated with cell biology techniques from a majority of 55 pediatric brain tumors samples, regardless of their histopathologies and grades of malignancy (57% of embryonal tumors, 57% of low-grade gliomas and neuro-glial tumors, 70% of ependymomas, 91% of high-grade gliomas). Most high-grade glioma-derived oncospheres (10/12) sustained long-term self-renewal akin to neural stem cells (>7 self-renewals), whereas cells with limited renewing abilities akin to neural progenitors dominated in all other tumors. Regardless of tumor entities, the young age group was associated with self-renewal properties akin to neural stem cells (P = 0.05, chi-square test). Survival analysis of the cohort showed an association between isolation of cells with long-term self-renewal abilities and a higher patient mortality rate (P = 0.013, log-rank test). Sampling of low- and high-grade glioma cultures showed that self-renewing cells forming oncospheres shared a molecular profile comprising embryonic and neural stem cell markers. Further characterization performed on subsets of high-grade gliomas and one low-grade glioma culture showed combination of this profile with mesenchymal markers, the radio-chemoresistance of the cells and the formation of aggressive tumors after intracerebral grafting. In brain tumors affecting adult patients, TSCs have been isolated only from high-grade gliomas. In contrast, our data show that tumor cells with stem cell-like or progenitor-like properties can be isolated from a wide range of histological sub-types and grades of pediatric brain tumors. They suggest that cellular mechanisms fueling tumor development differ between adult and pediatric brain tumors.
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影响因子：
3.7
作者：
Brennan C;Momota H;Hambardzumyan D;Ozawa T;Tandon A;Pedraza A;Holland E
通讯作者：
Holland E
影响因子：
3.7
作者：
Bax DA;Little SE;Gaspar N;Perryman L;Marshall L;Viana-Pereira M;Jones TA;Williams RD;Grigoriadis A;Vassal G;Workman P;Sheer D;Reis RM;Pearson AD;Hargrave D;Jones C
通讯作者：
Jones C
影响因子：
8
作者：
Guenther, H. S.;Schmidt, N. O.;Lamszus, K.
通讯作者：
Lamszus, K.
影响因子：
2.5
作者：
Brown, JP;Couillard-Després, S;Kuhn, HG
通讯作者：
Kuhn, HG
影响因子：
50.3
作者：
Chen, Ruihuan;Nishimura, Merry C.;Phillips, Heidi S.
通讯作者：
Phillips, Heidi S.