title: Populational equilibrium through exosome-mediated Wnt signaling in tumor progression of diffuse large B-cell lymphoma.
abstract: 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.
authors.affiliation: Department of Hematology and Oncology, Georg-August-University, Goettingen, Germany;
authors.forename: Raphael
authors.initials: R
authors.lastname: Koch
authors.forename: Martin
authors.initials: M
authors.lastname: Demant
authors.forename: Thiha
authors.initials: T
authors.lastname: Aung
authors.forename: Nina
authors.initials: N
authors.lastname: Diering
authors.forename: Anna
authors.initials: A
authors.lastname: Cicholas
authors.forename: Bjoern
authors.initials: B
authors.lastname: Chapuy
authors.forename: Dirk
authors.initials: D
authors.lastname: Wenzel
authors.forename: Marlen
authors.initials: M
authors.lastname: Lahmann
authors.forename: Annemarie
authors.initials: A
authors.lastname: Güntsch
authors.forename: Christina
authors.initials: C
authors.lastname: Kiecke
authors.forename: Sabrina
authors.initials: S
authors.lastname: Becker
authors.forename: Timo
authors.initials: T
authors.lastname: Hupfeld
authors.forename: Vivek
authors.initials: V
authors.lastname: Venkataramani
authors.forename: Marita
authors.initials: M
authors.lastname: Ziepert
authors.forename: Lennart
authors.initials: L
authors.lastname: Opitz
authors.forename: Wolfram
authors.initials: W
authors.lastname: Klapper
authors.forename: Lorenz
authors.initials: L
authors.lastname: Trümper
authors.forename: Gerald G
authors.initials: GG
authors.lastname: Wulf
mesh_terms: D002452:Cell Count; D049109:Cell Proliferation; D002999:Clone Cells / Q000473:pathology*; D018450:Disease Progression; D055354:Exosomes / Q000502:physiology*; D057809:HEK293 Cells; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000473:pathology*; D021381:Protein Transport; D014407:Tumor Cells, Cultured; D060449:Wnt Signaling Pathway / Q000502:physiology*