1. Populational equilibrium through exosome-mediated Wnt signaling in tumor progression of diffuse large B-cell lymphoma
- Author
-
Christina Kiecke, Wolfram Klapper, Nina Diering, Gerald Wulf, Lennart Opitz, Bjoern Chapuy, Lorenz Trümper, Raphael Koch, Sabrina Becker, Vivek Venkataramani, Timo Hupfeld, Thiha Aung, Marlen Lahmann, Anna Cicholas, Martin Demant, Dirk Wenzel, Marita Ziepert, and Annemarie Güntsch
- Subjects
Immunology ,Population ,Cell Count ,Biology ,Exosomes ,Biochemistry ,Exosome ,03 medical and health sciences ,0302 clinical medicine ,Side population ,medicine ,Tumor Cells, Cultured ,Homeostasis ,Humans ,education ,Wnt Signaling Pathway ,030304 developmental biology ,Cell Proliferation ,0303 health sciences ,education.field_of_study ,Cell growth ,HEK 293 cells ,Wnt signaling pathway ,Cell Biology ,Hematology ,medicine.disease ,Cell biology ,Clone Cells ,Protein Transport ,HEK293 Cells ,Tumor progression ,030220 oncology & carcinogenesis ,Disease Progression ,Neoplastic Stem Cells ,Lymphoma, Large B-Cell, Diffuse ,Diffuse large B-cell lymphoma - Abstract
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.
- Published
- 2014