Populational equilibrium through exosome-mediated Wnt signaling in tumor progression of diffuse large B-cell lymphoma

Tumors are composed of phenotypically heterogeneous cell populations. The nongenomic 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 (...

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Bibliographic Details
Published in:Blood 2014-04, Vol.123 (14), p.2189-2198
Main Authors: Koch, Raphael, Demant, Martin, Aung, Thiha, Diering, Nina, Cicholas, Anna, Chapuy, Bjoern, Wenzel, Dirk, Lahmann, Marlen, Güntsch, Annemarie, Kiecke, Christina, Becker, Sabrina, Hupfeld, Timo, Venkataramani, Vivek, Ziepert, Marita, Opitz, Lennart, Klapper, Wolfram, Trümper, Lorenz, Wulf, Gerald G.
Format: Article
Language:English
Subjects:
Cell Count
Cell Proliferation
Clone Cells - pathology
Disease Progression
Exosomes - physiology
HEK293 Cells
Homeostasis - physiology
Humans
Lymphoma, Large B-Cell, Diffuse - metabolism
Lymphoma, Large B-Cell, Diffuse - pathology
Neoplastic Stem Cells - pathology
Protein Transport
Tumor Cells, Cultured
Wnt Signaling Pathway - physiology
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Summary:Tumors are composed of phenotypically heterogeneous cell populations. The nongenomic 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. •Diffuse large B-cell lymphomas are composed of clonogenic side population (SP) cells and non-SP cells organized in a dynamic equilibrium.•Exosome-mediated Wnt signaling modulates transitions of cell states and tumor progression amenable to drug targeting.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2013-08-523886