Identification of a cancer stem cell in human brain tumors.
Identification of a cancer stem cell in human brain tumors.
复制标题
DOI：
--
复制
发表时间：
2003-09
期刊：
影响因子：
11.2
通讯作者：
Sheila K. Singh;I. Clarke;Mizuhiko Terasaki;Victoria E Bonn;C. Hawkins;J. Squire;P. Dirks
中科院分区：
文献类型：
--
作者：
Sheila K. Singh;I. Clarke;Mizuhiko Terasaki;Victoria E Bonn;C. Hawkins;J. Squire;P. Dirks
目前对人类脑肿瘤的大多数研究都集中在对大块肿瘤块的分子和细胞分析上。然而，有压倒性的证据表明，在一些恶性肿瘤中，肿瘤克隆在增殖和分化方面是异质的。在人类白血病中，肿瘤克隆被组织为一个层次，其起源于具有广泛增殖和自我更新潜力的罕见白血病干细胞，并负责维持肿瘤克隆。我们在这里报告的识别和纯化的癌症干细胞从人脑肿瘤的不同表型，具有显着的增殖能力，自我更新和分化。与低级别胶质瘤相比，在最具侵袭性的髓母细胞瘤临床样本中，脑肿瘤干细胞（BTSC）的自我更新能力最高。BTSC仅与表达神经干细胞表面标志物CD 133的细胞级分分离。这些CD133+细胞可以在培养物中分化成与患者肿瘤表型相似的肿瘤细胞。BTSC的鉴定为研究中枢神经系统中的致瘤过程和开发靶向BTSC的治疗提供了有力的工具。
Most current research on human brain tumors is focused on the molecular and cellular analysis of the bulk tumor mass. However, there is overwhelming evidence in some malignancies that the tumor clone is heterogeneous with respect to proliferation and differentiation. In human leukemia, the tumor clone is organized as a hierarchy that originates from rare leukemic stem cells that possess extensive proliferative and self-renewal potential, and are responsible for maintaining the tumor clone. We report here the identification and purification of a cancer stem cell from human brain tumors of different phenotypes that possesses a marked capacity for proliferation, self-renewal, and differentiation. The increased self-renewal capacity of the brain tumor stem cell (BTSC) was highest from the most aggressive clinical samples of medulloblastoma compared with low-grade gliomas. The BTSC was exclusively isolated with the cell fraction expressing the neural stem cell surface marker CD133. These CD133+ cells could differentiate in culture into tumor cells that phenotypically resembled the tumor from the patient. The identification of a BTSC provides a powerful tool to investigate the tumorigenic process in the central nervous system and to develop therapies targeted to the BTSC.