Format

Send to

Choose Destination
Cell. 2010 May 14;141(4):583-94. doi: 10.1016/j.cell.2010.04.020.

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

Author information

1
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.

Abstract

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.

Comment in

PMID:
20478252
PMCID:
PMC2882693
DOI:
10.1016/j.cell.2010.04.020
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center