Identification of CD15 as a marker for tumor-propagating cells in a mouse model of medulloblastoma.
Identification of CD15 as a marker for tumor-propagating cells in a mouse model of medulloblastoma.
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DOI：
10.1016/j.ccr.2008.12.016
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发表时间：
2009-02-03
期刊：
影响因子：
50.3
通讯作者：
Wechsler-Reya RJ
中科院分区：
文献类型：
--
作者：
Read TA;Fogarty MP;Markant SL;McLendon RE;Wei Z;Ellison DW;Febbo PG;Wechsler-Reya RJ
许多癌症的生长依赖于称为癌症干细胞或肿瘤增殖细胞（TPC）的自我更新细胞。在人脑肿瘤中，表达干细胞标志物CD 133的细胞被认为是TPC。在这里，我们表明，肿瘤的髓母细胞瘤模型，补丁突变小鼠，不是由CD 133+细胞，但由细胞表达的祖标记Math 1和CD 15/SSEA-1。这些细胞具有不同的表达谱，表明增殖能力增加，经历凋亡和分化的趋势降低。CD 15也存在于人髓母细胞瘤的一个亚群中，并且表达与在鼠CD 15+细胞中发现的基因相似的基因的肿瘤具有较差的预后。因此，CD 15可能是髓母细胞瘤中TPC的重要标志物。尽管在人脑肿瘤中已经描述了肿瘤增殖细胞，但在该疾病的小鼠模型中尚未鉴定出此类细胞。在小鼠模型中发现TPC是至关重要的，因为它允许研究它们的发育起源，以及在物种匹配的微环境中对这些细胞进行实验操作和靶向。在这里，我们在髓母细胞瘤模型中鉴定了一群TPC，并表明这些细胞表达CD 15（也称为SSEA-1或LeX），类似于神经祖细胞。我们的数据挑战了所有脑肿瘤都是由干细胞样细胞繁殖的概念，并提高了CD 15可用于识别和靶向人类脑肿瘤中TPC的可能性。
The growth of many cancers depends on self-renewing cells called cancer stem cells or tumor-propagating cells (TPCs). In human brain tumors, cells expressing the stem cell marker CD133 have been implicated as TPCs. Here we show that tumors from a model of medulloblastoma, the Patched mutant mouse, are not propagated by CD133+ cells but by cells expressing the progenitor markers Math1 and CD15/SSEA-1. These cells have a distinct expression profile that suggests increased proliferative capacity and decreased tendency to undergo apoptosis and differentiation. CD15 is also found in a subset of human medulloblastomas, and tumors expressing genes similar to those found in murine CD15+ cells have a poorer prognosis. Thus, CD15 may represent an important marker for TPCs in medulloblastoma. Although tumor-propagating cells have been described in human brain tumors, such cells have not been identified in mouse models of the disease. Finding TPCs in mouse models is critical because it allows studies of their developmental origins, and experimental manipulation and targeting of these cells in a species-matched microenvironment. Here we identify a population of TPCs in a model of medulloblastoma, and show that these cells express CD15 (also known as SSEA-1 or LeX) and resemble neural progenitors. Our data challenge the notion that all brain tumors are propagated by stem-like cells, and raise the possibility that CD15 may be used to identify and target TPCs in human brain tumors.
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DOI：
10.1016/s0736-5748(97)00036-1
发表时间：
1997-11-01
影响因子：
1.8
作者：
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通讯作者：
Mai, JK
影响因子：
20.3
作者：
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影响因子：
56.9
作者：
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通讯作者：
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影响因子：
64.8
作者：
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通讯作者：
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影响因子：
25
作者：
Lee, A;Kessler, JD;Wechsler-Reya, RJ
通讯作者：
Wechsler-Reya, RJ