Identification of human brain tumour initiating cells
Identification of human brain tumour initiating cells
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DOI：
10.1038/nature03128
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发表时间：
2004-11-18
期刊：
影响因子：
64.8
通讯作者：
Dirks, PB
中科院分区：
文献类型：
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作者：
Singh, SK;Hawkins, C;Dirks, PB
癌症干细胞(CSC)假说表明，肿瘤克隆仅由极少数具有干细胞特性的细胞(1，2)维持。尽管CSCs在人类白血病中的存在已被证实(3，4)，但除了乳腺癌外，在实体肿瘤中几乎没有CSCs的证据(5)。最近，我们前瞻性地从体外表现出干细胞特性的人脑肿瘤中分离出CD133(+)细胞亚群。然而，CSCs的真正衡量标准是它们自我更新和准确重现原始肿瘤的能力(1，2，7)。在这里，我们报告了一种异种移植试验的发展，该试验确定了体内启动肿瘤的人脑肿瘤起始细胞。只有CD133(+)脑瘤部分包含能够在NOD-SCID(非肥胖糖尿病，严重联合免疫缺陷)小鼠脑中启动肿瘤的细胞。注射100个CD133(+)细胞产生的肿瘤可以连续移植，是患者原始肿瘤的表型，而注射105个CD133(-)细胞植入但不会导致肿瘤。因此，脑肿瘤起始细胞的识别为人类脑肿瘤的发病机制提供了洞察力，为CSC假说作为许多实体肿瘤的基础提供了强有力的支持(5)，并为更有效的癌症治疗建立了以前未确定的细胞靶点。
The cancer stem cell (CSC) hypothesis suggests that neoplastic clones are maintained exclusively by a rare fraction of cells with stem cell properties(1,2). Although the existence of CSCs in human leukaemia is established(3,4), little evidence exists for CSCs in solid tumours, except for breast cancer(5). Recently, we prospectively isolated a CD133(+) cell subpopulation from human brain tumours that exhibited stem cell properties in vitro(6). However, the true measures of CSCs are their capacity for self renewal and exact recapitulation of the original tumour(1,2,7). Here we report the development of a xenograft assay that identified human brain tumour initiating cells that initiate tumours in vivo. Only the CD133(+) brain tumour fraction contains cells that are capable of tumour initiation in NOD-SCID (non-obese diabetic, severe combined immunodeficient) mouse brains. Injection of as few as 100 CD133(+) cells produced a tumour that could be serially transplanted and was a phenocopy of the patient's original tumour, whereas injection of 10 5 CD133(-) cells engrafted but did not cause a tumour. Thus, the identification of brain tumour initiating cells provides insights into human brain tumour pathogenesis, giving strong support for the CSC hypothesis as the basis for many solid tumours(5), and establishes a previously unidentified cellular target for more effective cancer therapies.