Human melanoma-initiating cells express neural crest nerve growth factor receptor CD271.
Human melanoma-initiating cells express neural crest nerve growth factor receptor CD271.
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人类黑色素瘤中是否存在致瘤性癌症干细胞的问题最近出现。在这里，我们表明，在黑色素瘤中，肿瘤干细胞（MTSC）可以作为一个高度富集的CD 271 + MTSC人口使用的过程中，最大限度地提高了活细胞移植的前瞻性分离。在这项研究中，肿瘤样本取自广泛的部位和阶段。将重悬于基质胶载体中的高活力FACS分离细胞植入T、B和NK缺陷型Rag 2 −/− γc−/−小鼠（RG）小鼠。CD 271+细胞亚群是测试的9/10个黑素瘤中的肿瘤起始群体。将分离的黑色素瘤细胞移植到RG小鼠的移植人皮肤或骨骼中，导致来自CD 271+而不是CD 271 −细胞的黑色素瘤。我们还表明，由CD 271+患者细胞移植的肿瘤能够在体内转移。重要的是，在86%、69%和68%的黑色素瘤患者中，CD 271+黑色素瘤细胞分别缺乏TYR、MART和法师的表达，这表明为什么针对这些抗原的T细胞疗法通常仅导致暂时的肿瘤缩小。
The question whether tumorigenic cancer stem cells exist in human melanomas has arisen recently. Here we show that in melanomas, tumor stem cells (MTSC) can be isolated prospectively as a highly enriched CD271+ MTSC population using a process that maximizes viable cell transplantation. In this study the tumors sampled were taken from a broad spectrum of sites and stages. High viability FACS isolated cells resuspended in a matrigel vehicle were implanted into T, B, and NK deficient Rag2−/− γc−/− mice (RG) mice. The CD271+ subset of cells was the tumor initiating population in 9/10 melanomas tested. Transplantation of isolated melanoma cells into engrafted human skin or bone in RG mice resulted in melanoma from CD271+ but not CD271− cells. We also showed that tumors transplanted by CD271+ patient cells were capable of metastasis in-vivo. Importantly, CD271+ melanoma cells lacked expression of TYR, MART and MAGE in 86%, 69% and 68% of melanoma patients respectively suggesting why T cell therapies directed at these antigens usually result in only temporary tumor shrinkage.
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DOI：
10.1073/pnas.0906549106
发表时间：
2009-08-18
影响因子：
11.1
作者：
Chan, Keith Syson;Espinosa, Inigo;Weissman, Irving L.
通讯作者：
Weissman, Irving L.
影响因子：
158.5
作者：
Jamieson, CHM;Ailles, LE;Weissman, IL
通讯作者：
Weissman, IL
影响因子：
64.8
作者：
O'Brien, Catherine A.;Pollett, Aaron;Dick, John E.
通讯作者：
Dick, John E.
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.
DOI：
10.1016/s0190-9622(96)90728-8
发表时间：
1996-11-01
影响因子：
13.8
作者：
Iwamoto, S;Odland, PB;Bothwell, M
通讯作者：
Bothwell, M