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Cancer Cell. 2013 Jan 14;23(1):77-92. doi: 10.1016/j.ccr.2012.12.003.

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.

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1
Department of Hematology, Oncology, Technical University, 81675 Munich, Germany.

Abstract

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.

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PMID:
23328482
PMCID:
PMC3546417
DOI:
10.1016/j.ccr.2012.12.003
[Indexed for MEDLINE]
Free PMC Article

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