Cell
Volume 141, Issue 4, 14 May 2010, Pages 583-594
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Article
A Temporarily Distinct Subpopulation of Slow-Cycling Melanoma Cells Is Required for Continuous Tumor Growth

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Summary

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.

Highlights

► The H3K4 demethylase JARID1B marks a subpopulation of slow-cycling melanoma cells ► The JARID1B+ subpopulation is required for continuous tumor maintenance ► Cells can lose or gain JARID1B expression and do not follow a stem cell hierarchy ► Tumor initiation is not necessarily linked with tumor maintenance

HUMDISEASE
STEMCELL

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