Protein Kinase C-β-Dependent Activation of NF-κB in Stromal Cells Is Indispensable for the Survival of Chronic Lymphocytic Leukemia B Cells In Vivo

被引：117

作者：

Lutzny, Gloria ^{[1
]}

Kocher, Thomas ^{[4
]}

Schmidt-Supprian, Marc ^{[5
]}

Rudelius, Martina ^{[2
]}

Klein-Hitpass, Ludger ^{[6
]}

Finch, Andrew J. ^{[8
,9
]}

Duerig, Jan ^{[7
]}

Wagner, Michaela ^{[1
]}

Haferlach, Claudia ^{[10
]}

Kohlmann, Alexander ^{[10
]}

Schnittger, Susanne ^{[10
]}

Seifert, Marc ^{[6
]}

Wanninger, Stefan ^{[3
]}

Zaborsky, Nadja ^{[4
]}

Oostendorp, Robert ^{[1
]}

Ruland, Juergen ^{[3
]}

Leitges, Michael ^{[11
]}

Kuhnt, Toni ^{[1
]}

Schaefer, Yvonne ^{[1
]}

Lampl, Benedikt ^{[1
]}

Peschel, Christian ^{[1
]}

Egle, Alexander ^{[4
]}

Ringshausen, Ingo ^{[1
]}

机构：

[1] Tech Univ, Dept Hematol, D-81675 Munich, Germany

[2] Tech Univ, Dept Pathol, D-81675 Munich, Germany

[3] Tech Univ, Inst Klin Chem & Pathobiochem, D-81675 Munich, Germany

[4] Paracelsus Private Med Univ Hosp, Med Dept Hematol 3, Lab Immunol & Mol Canc Res, A-5020 Salzburg, Austria

[5] Max Planck Inst Biochem, D-82152 Martinsried, Germany

[6] Univ Duisburg Essen, Fac Med, Inst Cell Biol Canc Res, D-45122 Essen, Germany

[7] Univ Duisburg Essen, Dept Hematol, D-45122 Essen, Germany

[8] Med Res Council Lab Mol Biol, Cambridge CB2 0QH, England

[9] Univ Cambridge, Dept Haematol, Cambridge CB2 0XY, England

[10] MLL Munich Leukemia Lab, D-81377 Munich, Germany

[11] Biotechnol Ctr Oslo, N-0317 Oslo, Norway

来源：

CANCER CELL | 2013年 / 23卷 / 01期

基金：

奥地利科学基金会;

关键词：

EXPRESSION; APOPTOSIS; MOUSE; CLL; MODEL; DEGRADATION; RECRUITMENT; RESISTANCE; INHIBITOR; MUTATIONS;

D O I：

10.1016/j.ccr.2012.12.003

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Tumor cell survival critically depends on heterotypic communication with benign cells in the microenvironrnent. Here, we describe a survival signaling pathway activated in stromal cells by contact to B cells from patients with chronic lymphocytic leukemia (CLL). The expression of protein kinase C (PKC)-beta II and the subsequent activation of NF-kappa B in bone marrow stromal cells are prerequisites to support the survival of malignant B cells. PKC-beta knockout mice are insusceptible to CLL transplantations, underscoring the in vivo significance of the PKC-beta II-NF-kappa B signaling pathway in the tumor microenvironment. Upregulated stromal PKG-beta II in biopsies from patients with CLL, acute lymphoblastic leukemia, and mantle cell lymphoma suggests that this pathway may commonly be activated in a variety of hematological malignancies.

引用

页码：77 / 92

页数：16

共 50 条

[1] Protein kinase C-β-dependent changes in the glucose metabolism of bone marrow stromal cells of chronic lymphocytic leukemia
von Heydebrand, Franziska
Fuchs, Maximilian
Kunz, Meik
Voelkl, Simon
Kremer, Anita N.
Oostendorp, Robert A. J.
Wilke, Jochen
Leitges, Michael
Egle, Alexander
Mackensen, Andreas
Lutzny-Geier, Gloria
STEM CELLS, 2021, 39 (06) : 819 - 830
[2] A sustained activation of PI3K/NF-κB pathway is critical for the survival of chronic lymphocytic leukemia B cells
S Cuní
P Pérez-Aciego
G Pérez-Chacón
J A Vargas
A Sánchez
F M Martín-Saavedra
S Ballester
J García-Marco
J Jordá
A Durántez
Leukemia, 2004, 18 : 1391 - 1400
[3] Activation of the B-cell receptor successively activates NF-κB and STAT3 in chronic lymphocytic leukemia cells
Rozovski, Uri
Harris, David M.
Li, Ping
Liu, Zhiming
Jain, Preetesh
Veletic, Ivo
Ferrajoli, Alessandra
Burger, Jan
Thompson, Philip
Jain, Nitin
Wierda, William
Keating, Michael J.
Estrov, Zeev
INTERNATIONAL JOURNAL OF CANCER, 2017, 141 (10) : 2076 - 2081
[4] Targeting metabolism and survival in chronic lymphocytic leukemia and Richter syndrome cells by a novel NF-κB inhibitor
Vaisitti, Tiziana
Gaudino, Federica
Ouk, Samedy
Moscvin, Maria
Vitale, Nicoletta
Serra, Sara
Arruga, Francesca
Zakrzewski, Johannes L.
Liou, Hsiou-Chi
Allan, John N.
Furman, Richard R.
Deaglio, Silvia
HAEMATOLOGICA, 2017, 102 (11) : 1878 - 1889
[5] STAT-3 Activates NF-κB in Chronic Lymphocytic Leukemia Cells
Liu, Zhiming
Hazan-Halevy, Inbal
Harris, David M.
Li, Ping
Ferrajoli, Alessandra
Faderl, Stefan
Keating, Michael J.
Estrov, Zeev
MOLECULAR CANCER RESEARCH, 2011, 9 (04) : 507 - 515
[6] NF-κB as a therapeutic target in chronic lymphocytic leukemia
Lopez-Guerra, Monica
Colomer, Dolors
EXPERT OPINION ON THERAPEUTIC TARGETS, 2010, 14 (03) : 275 - 288
[7] Stereotypical Chronic Lymphocytic Leukemia B-Cell Receptors Recognize Survival Promoting Antigens on Stromal Cells
Binder, Mascha
Lechenne, Barbara
Ummanni, Ramesh
Scharf, Christan
Balabanov, Stefan
Trusch, Maria
Schlueter, Hartmut
Braren, Ingke
Spillner, Edzard
Trepel, Martin
PLOS ONE, 2010, 5 (12):
[8] NF-κB activation in chronic lymphocytic leukemia: A point of convergence of external triggers and intrinsic lesions
Mansouri, Larry
Papakonstantinou, Nikos
Ntoufa, Stavroula
Stamatopoulos, Kostas
Rosenquist, Richard
SEMINARS IN CANCER BIOLOGY, 2016, 39 : 40 - 48
[9] Constitutive activation of NF-κB signaling by NOTCH1 mutations in chronic lymphocytic leukemia
Xu, Zhen-Shu
Zhang, Ju-Shun
Zhang, Jing-Yan
Wu, Shun-Quan
Xiong, Dong-Lian
Chen, Hui-Jun
Chen, Zhi-Zhe
Zhan, Rong
ONCOLOGY REPORTS, 2015, 33 (04) : 1609 - 1614
[10] HuR Affects Proliferation and Apoptosis of Chronic Lymphocytic Leukemia Cells via NF-κB Pathway
Xiao, Kai
Yang, Lin
Gao, Xinfeng
An, Ying
Xie, Wei
Jingquan, Guo
BIOMED RESEARCH INTERNATIONAL, 2020, 2020

← 1 2 3 4 5 →