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.

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.

• Authors: Gloria Lutzny, Thomas Kocher, Marc Schmidt-Supprian, Martina Rudelius, Ludger Klein-Hitpass, Andrew J Finch, Jan Dürig, Michaela Wagner, Claudia Haferlach, Alexander Kohlmann, Susanne Schnittger, Marc Seifert, Stefan Wanninger, Nadja Zaborsky, Robert Oostendorp, Jürgen Ruland, Michael Leitges, Toni Kuhnt, Yvonne Schäfer, Benedikt Lampl, Christian Peschel, Alexander Egle, Ingo Ringshausen
• Journal: Cancer cell (Cancer Cell) Vol. 23 Issue 1 Pg. 77-92 (Jan 14 2013) ISSN: 1878-3686 [Electronic] United States
• PMID: 23328482 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Cytokines
• NF-kappa B
• Protein Kinase C
• Protein Kinase C beta

Topics

• Animals
• B-Lymphocytes (metabolism, pathology)
• Cytokines (metabolism)
• Gene Expression Regulation, Neoplastic
• Humans
• Leukemia, Lymphocytic, Chronic, B-Cell (metabolism, pathology)
• Mice
• Mice, Knockout
• Mice, Transgenic
• NF-kappa B (genetics, metabolism)
• Protein Kinase C (genetics, metabolism, physiology)
• Protein Kinase C beta
• Signal Transduction
• Stromal Cells (metabolism)
• Tumor Microenvironment