A Temporarily Distinct Subpopulation of Slow-Cycling Melanoma Cells Is Required for Continuous Tumor Growth

Roesch, Alexander and Fukunaga-Kalabis, Mizuho and Schmidt, Elizabeth C. and Zabierowski, Susan E. and Brafford, Patricia A. and Vultur, Adina and Basu, Devraj and Gimotty, Phyllis and Vogt, Thomas and Herlyn, Meenhard (2010) A Temporarily Distinct Subpopulation of Slow-Cycling Melanoma Cells Is Required for Continuous Tumor Growth. CELL, 141 (4). pp. 583-594. ISSN 0092-8674, 1097-4172

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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.

Item Type: Article
Uncontrolled Keywords: CANCER STEM-CELLS; TRANSCRIPTIONAL REPRESSION; METASTATIC MELANOMA; BREAST-CANCER; BINDING; PLU-1; IDENTIFICATION; PROGRESSION; EXPRESSION; LEUKEMIA;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Dermatologie und Venerologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 30 Jul 2020 11:06
Last Modified: 30 Jul 2020 11:06
URI: https://pred.uni-regensburg.de/id/eprint/24732

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