Bone marrow fibroblasts induce expression of PI3K/NF-κB pathway genes and a pro-angiogenic phenotype in CLL cells

被引:58
作者
Edelmann, J. [1 ]
Klein-Hitpass, L. [2 ]
Carpinteiro, A. [1 ,3 ]
Fuehrer, A. [1 ]
Sellmann, L. [1 ,2 ]
Stilgenbauer, S. [4 ]
Duehrsen, U. [1 ]
Duerig, J. [1 ]
机构
[1] Univ Duisburg Essen, Univ Hosp, Dept Hematol, D-45122 Essen, Germany
[2] Univ Duisburg Essen, Univ Hosp, Inst Cell Biol, D-45122 Essen, Germany
[3] Univ Duisburg Essen, Univ Hosp, Inst Mol Biol, D-45122 Essen, Germany
[4] Univ Ulm, Ulm, Germany
关键词
CLL; hematopoietic microenvironment; neoangiogenesis; osteopontin;
D O I
10.1016/j.leukres.2008.03.003
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Microarray-based gene expression profiling (GEP) was used to study how stroma modulates the survival of CLL cells in an in vitro coculture model employing the murine fibroblast cell line M2-10B4. CLL cells cultured in direct contact with the stromal layer (STR) showed a significantly better survival than cells cultured in transwell (TW) inserts above the M2-10B4 cells. STR as compared to TW conditions induced a significant up-regulation of PI3K/NF-kappa B pro-survival pathway genes and mediated a pro-angiogenetic switch in the CLL cells by up-regulation of vascular endothelial growth factor (VEGF) and osteopontin (OPN) and down-regulation of the anti-angiogenefic molecule thrombospondin-1 (TSP-1). (c) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1565 / 1572
页数:8
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