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

被引：99

作者：

Koch, Raphael ^{[1
]}

Demant, Martin ^{[1
]}

Aung, Thiha ^{[1
]}

Diering, Nina ^{[1
]}

Cicholas, Anna ^{[1
]}

Chapuy, Bjoern ^{[2
]}

Wenzel, Dirk ^{[3
]}

Lahmann, Marlen ^{[1
]}

Guentsch, Annemarie ^{[1
]}

Kiecke, Christina ^{[1
]}

Becker, Sabrina ^{[1
]}

Hupfeld, Timo ^{[1
]}

Venkataramani, Vivek ^{[1
]}

Ziepert, Marita ^{[4
]}

Opitz, Lennart ^{[5
]}

Klapper, Wolfram ^{[6
,7
]}

Truemper, Lorenz ^{[1
]}

Wulf, Gerald G. ^{[1
]}

机构：

[1] Univ Gottingen, Dept Hematol & Oncol, D-37075 Gottingen, Germany

[2] Dana Farber Canc Inst, Boston, MA 02115 USA

[3] Max Planck Inst Biophys Chem, D-37077 Gottingen, Germany

[4] Inst Med Informat Stat & Epidemiol, Leipzig, Germany

[5] Funct Genom Ctr Zurich, Zurich, Switzerland

[6] Hematopathol Sect, Kiel, Germany

[7] Lymph Node Registry, Kiel, Germany

来源：

BLOOD | 2014年 / 123卷 / 14期

关键词：

ACUTE MYELOID-LEUKEMIA; HEMATOPOIETIC STEM-CELLS; DRUG EFFLUX CAPACITY; BETA-CATENIN; SIDE POPULATION; ELDERLY-PATIENTS; TRANSPORTER A3; GROWTH-FACTORS; CANCER-CELLS; IN-VIVO;

D O I：

10.1182/blood-2013-08-523886

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：2189 / 2198

页数：10

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