A temporarily distinct subpopulation of slow-cycling melanoma cells is required for continuous tumor growth.
A temporarily distinct subpopulation of slow-cycling melanoma cells is required for continuous tumor growth.
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DOI：
10.1016/j.cell.2010.04.020
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发表时间：
2010-05-14
期刊：
影响因子：
64.5
通讯作者：
Herlyn M
中科院分区：
文献类型：
--
作者：
Roesch A;Fukunaga-Kalabis M;Schmidt EC;Zabierowski SE;Brafford PA;Vultur A;Basu D;Gimotty P;Vogt T;Herlyn M
黑色素瘤是一种高度异质性的肿瘤，但其不同亚群的生物学意义尚不清楚。使用H3K4去甲基化酶JARID1B （KDM5B/ plu1 /RBP2-H1）作为生物标志物，我们已经表征了一个小的慢循环黑色素瘤细胞亚群，在快速增殖的主要群体中，其周期为bb0 4周的两倍。分离的jarid1b阳性黑色素瘤细胞产生高度增殖的后代。JARID1B的敲除导致肿瘤生长的初始加速，随后衰竭，这表明JARID1B阳性亚群对肿瘤的持续生长至关重要。JARID1B的表达是动态调节的，不遵循分层的癌症干细胞模型，因为JARID1B阴性细胞可以变为阳性，甚至单个黑色素瘤细胞无论选择如何都具有致瘤性。这些结果提示了对黑色素瘤异质性的新认识，肿瘤维持是一个由暂时不同的亚群介导的动态过程。
Melanomas are highly heterogeneous tumors, but the biological significance of their different subpopulations is not clear. Using the H3K4 demethylase JARID1B (KDM5B/PLU-1/RBP2-H1) as a biomarker, we have characterized a small subpopulation of slow-cycling melanoma cells that cycle with doubling times of >4 weeks within the rapidly proliferating main population. Isolated JARID1B-positive melanoma cells give rise to a highly proliferative progeny. Knock-down of JARID1B leads to an initial acceleration of tumor growth followed by exhaustion which suggests that the JARID1B-positive subpopulation is essential for continuous tumor growth. Expression of JARID1B is dynamically regulated and does not follow a hierarchical cancer stem cell model because JARID1B-negative cells can become positive and even single melanoma cells irrespective of selection are tumorigenic. These results suggest a new understanding of melanoma heterogeneity with tumor maintenance as a dynamic process mediated by a temporarily distinct subpopulation.
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主动Notch1将转化的表型赋予原代人黑色素细胞。
影响因子：
11.2
作者：
Pinnix CC;Lee JT;Liu ZJ;McDaid R;Balint K;Beverly LJ;Brafford PA;Xiao M;Himes B;Zabierowski SE;Yashiro-Ohtani Y;Nathanson KL;Bengston A;Pollock PM;Weeraratna AT;Nickoloff BJ;Pear WS;Capobianco AJ;Herlyn M
通讯作者：
Herlyn M
影响因子：
64.5
作者：
Klose, Robert J.;Yan, Qin;Kaelin, William G., Jr.
通讯作者：
Kaelin, William G., Jr.
影响因子：
8.4
作者：
Monzani, Elena;Facchetti, Floriana;La Porta, Caterina A. M.
通讯作者：
La Porta, Caterina A. M.
影响因子：
64.5
作者：
Guenther, Matthew G.;Levine, Stuart S.;Young, Richard A.
通讯作者：
Young, Richard A.
影响因子：
11.2
作者：
Liu, ZJ;Xiao, M;Herlyn, M
通讯作者：
Herlyn, M