Journal
BLOOD
Volume 123, Issue 14, Pages 2189-2198Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2013-08-523886
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Funding
- Deutsche Forschungsgemeinschaft [DFG Wu 310/3-1]
- University Medicine Goettingen
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Tumors are composed of phenotypically heterogeneous cell populations. The non-genomic mechanisms underlying transitions and interactions between cell populations are largely unknown. Here, we show that diffuse large B-cell lymphomas possess a self-organized infrastructure comprising side population (SP) and non-SP cells, where transitions between clonogenic states are modulated by exosome-mediated Wnt signaling. DNA methylation modulated SP-non-SP transitions and was correlated with the reciprocal expressions of Wnt signaling pathway agonist Wnt3a in SP cells and the antagonist secreted frizzled-related protein 4 in non-SP cells. Lymphoma SP cells exhibited autonomous clonogenicity and exported Wnt3a via exosomes to neighboring cells, thus modulating population equilibrium in the tumor.
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