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hany2007

A Temporarily Distinct Subpopulation3 Q) s$ E  D3 n
of Slow-Cycling Melanoma Cells
1 i, ?8 e% ?7 ?$ J, EIs Required for Continuous Tumor Growth0 [" J* t4 @" d2 {7 t

( }6 D! T/ [1 S$ Z6 CMelanomas 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
7 U: _& H3 X2 w8 N, E8 Hwhich 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.7 c* ?! k2 w8 l9 H. B7 ~

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