TY - JOUR
T1 - 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
AU - Lutzny, Gloria
AU - Kocher, Thomas
AU - Schmidt-Supprian, Marc
AU - Rudelius, Martina
AU - Klein-Hitpass, Ludger
AU - Finch, Andrew J.
AU - Dürig, Jan
AU - Wagner, Michaela
AU - Haferlach, Claudia
AU - Kohlmann, Alexander
AU - Schnittger, Susanne
AU - Seifert, Marc
AU - Wanninger, Stefan
AU - Zaborsky, Nadja
AU - Oostendorp, Robert
AU - Ruland, Jürgen
AU - Leitges, Michael
AU - Kuhnt, Toni
AU - Schäfer, Yvonne
AU - Lampl, Benedikt
AU - Peschel, Christian
AU - Egle, Alexander
AU - Ringshausen, Ingo
N1 - Funding Information:
We would like to thank Laura Soucek and Jonathan Whitfield for fruitful scientific discussions and their help with the manuscript. The research was supported by grants from the Deutschen Forschungsgemeinschaft (DFG, SFB-TRR54, TPC3) to I.R. and (DFG, SFB-TRR54, TPA3) to M.S.-S., and grants from the Austrian Science Fund (FWF) P19481-B12 and L488-B13 to A.E. and T516-B13 to N.Z. T. Kocher is a recipient of a DOC fellowship of the Austrian Academy of Sciences (23137).
PY - 2013/1/14
Y1 - 2013/1/14
N2 - Tumor cell survival critically depends on heterotypic communication with benign cells in the microenvironment. 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)-βII and the subsequent activation of NF-κB in bone marrow stromal cells are prerequisites to support the survival of malignant B cells. PKC-β knockout mice are insusceptible to CLL transplantations, underscoring the in vivo significance of the PKC-βII-NF-κB signaling pathway in the tumor microenvironment. Upregulated stromal PKC-βII 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.
AB - Tumor cell survival critically depends on heterotypic communication with benign cells in the microenvironment. 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)-βII and the subsequent activation of NF-κB in bone marrow stromal cells are prerequisites to support the survival of malignant B cells. PKC-β knockout mice are insusceptible to CLL transplantations, underscoring the in vivo significance of the PKC-βII-NF-κB signaling pathway in the tumor microenvironment. Upregulated stromal PKC-βII 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.
UR - https://www.scopus.com/pages/publications/84872387409
U2 - 10.1016/j.ccr.2012.12.003
DO - 10.1016/j.ccr.2012.12.003
M3 - Article
C2 - 23328482
AN - SCOPUS:84872387409
SN - 1535-6108
VL - 23
SP - 77
EP - 92
JO - Cancer Cell
JF - Cancer Cell
IS - 1
ER -