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

被引:56
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
相关论文
共 28 条
  • [1] Angiogenesis in acute and chronic leukemias and myelodysplastic syndromes
    Aguayo, A
    Kantarjian, H
    Manshouri, T
    Gidel, C
    Estey, E
    Thomas, D
    Koller, C
    Estrov, Z
    O'Brien, S
    Keating, M
    Freireich, E
    Albitar, M
    [J]. BLOOD, 2000, 96 (06) : 2240 - 2245
  • [2] Clinical relevance of Flt1 and Tie1 angiogenesis receptors expression in B-cell chronic lymphocytic leukemia (CLL)
    Aguayo, A
    Manshouri, T
    O'Brien, S
    Keating, M
    Beran, M
    Koller, C
    Kantarjian, H
    Rogers, A
    Albitar, M
    [J]. LEUKEMIA RESEARCH, 2001, 25 (04) : 279 - 285
  • [3] Homologous recombinational repair vis-a-vis chlorambucil resistance in chronic lymphocytic leukemia
    Bello, VE
    Aloyz, RS
    Christodoulopoulos, G
    Panasci, LC
    [J]. BIOCHEMICAL PHARMACOLOGY, 2002, 63 (09) : 1585 - 1588
  • [4] Involvement of regulatory and catalytic subunits of phosphoinositide 3-kinase in NF-κB activation
    Béraud, C
    Henzel, WJ
    Baeuerle, PA
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (02) : 429 - 434
  • [5] Burger JA, 2000, BLOOD, V96, P2655
  • [6] Role of the microenvironment in chronic lymphocytic leukaemia
    Caligaris-Cappio, F
    [J]. BRITISH JOURNAL OF HAEMATOLOGY, 2003, 123 (03) : 380 - 388
  • [7] The multifaceted roles of osteopontin in cell signaling, tumor progression and angiogenesis
    Chakraborty, Goutam
    Jain, Shalini
    Behera, Reeti
    Ahmed, Mansoor
    Sharma, Priyanka
    Kumar, Vinit
    Kundu, Gopal C.
    [J]. CURRENT MOLECULAR MEDICINE, 2006, 6 (08) : 819 - 830
  • [8] National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: Revised guidelines for diagnosis and treatment
    Cheson, BD
    Bennett, JM
    Grever, M
    Kay, N
    Keating, MJ
    OBrien, S
    Rai, KR
    [J]. BLOOD, 1996, 87 (12) : 4990 - 4997
  • [9] Christodoulopoulos G, 1999, CLIN CANCER RES, V5, P2178
  • [10] A sustained activation of PI3K/NF-κB pathway is critical for the survival of chronic lymphocytic leukemia B cells
    Cuní, S
    Pérez-Aciego, P
    Pérez-Chacón, G
    Vargas, JA
    Sánchez, A
    Martín-Saavedra, FM
    Ballester, S
    García-Marco, J
    Jordá, J
    Durántez, A
    [J]. LEUKEMIA, 2004, 18 (08) : 1391 - 1400