[HTML][HTML] A temporarily distinct subpopulation of slow-cycling melanoma cells is required for continuous tumor growth

A Roesch, M Fukunaga-Kalabis, EC Schmidt… - Cell, 2010 - cell.com
A Roesch, M Fukunaga-Kalabis, EC Schmidt, SE Zabierowski, PA Brafford, A Vultur, D Basu…
Cell, 2010cell.com
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 …
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.
cell.com