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

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