Efficient tumour formation by single human melanoma cells.
Efficient tumour formation by single human melanoma cells.
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DOI：
10.1038/nature07567
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发表时间：
2008-12-04
期刊：
影响因子：
64.8
通讯作者：
Morrison, Sean J.
中科院分区：
文献类型：
--
作者：
Quintana, Elsa;Shackleton, Mark;Sabel, Michael S.;Fullen, Douglas R.;Johnson, Timothy M.;Morrison, Sean J.
癌症生物学中的一个基本问题是，在人类癌症中，具有致瘤潜能的细胞是普遍存在还是罕见的。对包括黑色素瘤在内的多种癌症的研究表明，当移植到NOD/SCID小鼠体内时，只有极少数（0.1%到0.0001%）的人类癌细胞具有致瘤潜能。然而，NOD/SCID小鼠在多大程度上低估了具有致瘤潜能的人类癌细胞的频率一直不确定。在此我们表明，改良的异种移植实验条件，包括使用免疫缺陷程度更高的NOD/SCID IL2Rγnull小鼠，可以将致瘤性黑色素瘤细胞的检测率提高几个数量级。在有限稀释实验中，来自12名不同患者的约25%的未分选黑色素瘤细胞，包括直接从患者获取的原发性和转移性黑色素瘤细胞，在这些更宽松的条件下形成了肿瘤。在单细胞移植中，来自4名不同患者的平均27%的未分选黑色素瘤细胞形成了肿瘤。因此，异种移植实验的改良可以显著提高致瘤细胞的可检测频率，这表明在某些人类癌症中，致瘤细胞是普遍存在的。
A fundamental question in cancer biology is whether cells with tumorigenic potential are common or rare within human cancers. Studies on diverse cancers, including melanoma, have indicated that only rare human cancer cells (0.1% to 0.0001%) have tumorigenic potential when transplanted into NOD/SCID mice. However, the extent to which NOD/SCID mice underestimate the frequency of tumorigenic human cancer cells has been uncertain. Here we show that modified xenotransplantation assay conditions, including the use of more highly immunocompromised NOD/SCID IL2Rγnull mice, can increase the detection of tumorigenic melanoma cells by several orders-of-magnitude. In limiting dilution assays, approximately 25% of unselected melanoma cells from 12 different patients, including cells from primary and metastatic melanomas obtained directly from patients, formed tumors under these more permissive conditions. In single cell transplants, an average of 27% of unselected melanoma cells from four different patients formed tumors. Xenotransplantation assay modifications can therefore dramatically increase the detectable frequency of tumorigenic cells, demonstrating that they are common in some human cancers.
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影响因子：
64.8
作者：
O'Brien, Catherine A.;Pollett, Aaron;Dick, John E.
通讯作者：
Dick, John E.
影响因子：
2.2
作者：
Bonnefoix, T;Bonnefoix, P;Sotto, JJ
通讯作者：
Sotto, JJ
影响因子：
20.3
作者：
Cox, CV;Evely, RS;Blair, A
通讯作者：
Blair, A
影响因子：
11.2
作者：
Frank, NY;Margaryan, A;Frank, MH
通讯作者：
Frank, MH
DOI：
10.1073/pnas.0703478104
发表时间：
2007-06-12
影响因子：
11.1
作者：
Dalerba, Piero;Dylla, Scott J.;Clarke, Michael F.
通讯作者：
Clarke, Michael F.