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A Temporarily Distinct Subpopulation
# B# `; T; N! g, c+ r7 i5 P$ G' l, d6 _of Slow-Cycling Melanoma Cells/ {: w E" Y0 ]7 P* k
Is Required for Continuous Tumor Growth
2 U% I6 K. ^$ {) M/ l
( m7 U6 b9 _7 b# NMelanomas 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. Q* {2 ^+ O& R2 `2 @! c. X- ]
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.3 @/ s1 s2 S; j3 W9 @1 D9 @- j+ `
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