A Temporarily Distinct Subpopulation of Slow-Cycling Melanoma Cells Is Required for Continuous Tumor Growth

被引：890

作者：

Roesch, Alexander ^{[1
]}

Fukunaga-Kalabis, Mizuho ^{[1
]}

Schmidt, Elizabeth C. ^{[1
]}

Zabierowski, Susan E. ^{[1
]}

Brafford, Patricia A. ^{[1
]}

Vultur, Adina ^{[1
]}

Basu, Devraj ^{[1
,2
]}

Gimotty, Phyllis ^{[3
]}

Vogt, Thomas ^{[4
]}

Herlyn, Meenhard ^{[1
]}

机构：

[1] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA

[2] Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA

[3] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA

[4] Univ Regensburg, Med Ctr, Dept Dermatol, D-93053 Regensburg, Germany

来源：

CELL | 2010年 / 141卷 / 04期

关键词：

CANCER STEM-CELL; TRANSCRIPTIONAL REPRESSION; METASTATIC MELANOMA; GENE-EXPRESSION; BINDING; PLU-1; IDENTIFICATION; PROGRESSION; LEUKEMIA; REVEALS;

D O I：

10.1016/j.cell.2010.04.020

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. Knockdown 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.

引用

页码：583 / 594

页数：12