Identification of A2B5+CD133-tumor-initiating cells in adult human gliomas
Identification of A2B5+CD133-tumor-initiating cells in adult human gliomas
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DOI：
10.1227/01.neu.0000316019.28421.95
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发表时间：
2008-02-01
期刊：
影响因子：
4.8
通讯作者：
Bruce, Jeffrey N.
中科院分区：
文献类型：
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作者：
Ogden, Alfred T.;Waziri, Allen E.;Bruce, Jeffrey N.
目的：多项研究表明，人脑胶质瘤中含有少量具有干细胞样特征的细胞。有人提出，这些“癌症干细胞”可能是胶质瘤形成和复发的唯一原因。然而，人类胶质瘤也包含大量的细胞，这些细胞与分化程度更高的神经胶质前体细胞非常相似。动物模型研究表明，这些细胞也具有形成恶性胶质瘤的能力。方法：为了研究干细胞样细胞和祖细胞样细胞在人脑胶质瘤中的作用，我们用流式细胞术检测了肿瘤干细胞标志物CD133和胶质前体细胞标志物A2B5在25例肿瘤中的表达。我们发现，人类胶质瘤在很大比例的细胞中持续表达A2B5(61.7+/-3.8%，平均值的标准误差)。相反，CD133表达较少且不一致(14.8+/-3.6%，平均值的标准差)，几个胶质母细胞瘤含有极少或没有可检测到的CD133(+)细胞。当存在CD133(+)人群时，几乎完全包含在A2B5(+)人群中。因此，根据这些标记物，大多数胶质瘤可以分为三个不同的群体(A2B5(+)CD133(+)，A2B5(+)CD133(-)和A2B5(-)CD133(-))。为了测试这些群体的致瘤能力，我们通过荧光激活细胞分选法从6个肿瘤中分离出细胞，并将它们重新注射到裸鼠体内。结果：我们发现这些不同群体形成肿瘤的能力因分离的人类肿瘤标本而异。在6个人脑胶质瘤中，4个含有A2B5(+)/CD133(-)细胞，移植到裸鼠体内形成肿瘤，3个含有A2B5(+)/CD133(+)细胞形成肿瘤，只有1个胶质瘤含有A2B5(-)/CD133(-)细胞，具有成瘤能力。结论：这些结果表明，人脑胶质瘤含有多种具有成瘤能力的细胞，并特异性地鉴定出与CD133(+)细胞表型不同的致瘤A2B5(+)细胞群。
OBJECTIVE: Several studies have shown that human gliomas contain a small population of cells with stem cell-like features. It has been proposed that these "cancer stem cells" may be uniquely responsible for glioma formation and recurrence. However, human gliomas also contain an abundance of cells that closely resemble more differentiated glial progenitors. Animal model studies have shown that these cells also possess the capacity to form malignant gliomas.METHODS: To investigate the contributions of stem-like and progenitor-like cells in human gliomas, we used flow cytometry to characterize the expression of a cancer stem cell marker (CD133) and a glial progenitor marker (A2B5) in 25 tumors. We found that human gliomas consistently express A2B5 in a large percentage of cells (61.7 +/- 3.8%, standard error of the mean). In contrast, CD133 expression was less abundant and less consistent (14.8 +/- 3.6%, standard error of the mean), with several glioblastomas containing very few or no detectable CD133(+) cells. When present, the CD133(+) population was almost entirely contained within the A2B5(+) population. Thus, most gliomas could be divided into three distinct populations on the basis of these markers (A2B5(+)CD133(+), A2B5(+)CD133(-), and A2B5(-)CD133(-)). To test the tumorigenic potential of these populations, we separated cells from six tumors by fluorescence-activated cell sorting and reinjected them into nude rats.RESULTS: We found that the capacity for these different populations to form tumors varied depending on the human tumor specimen from which they were isolated. Of the six human gliomas tested, four contained A2B5(+)/CD133(-) cells that formed tumors when transplanted into nude rats, three contained A2B5(+)/CD133(+) cells that formed tumors, and only one glioma contained A2B5(-)/CD133(-) cells with the capacity to form tumors.CONCLUSION: Together, these results demonstrate that human gliomas contain multiple populations of cells with the capacity to form tumors and specifically identify a population of tumorigenic A2B5(+) cells that are phenotypically distinct from CD133(+) cells.