[PDF][PDF] 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

G Lutzny, T Kocher, M Schmidt-Supprian, M Rudelius… - Cancer cell, 2013 - cell.com
G Lutzny, T Kocher, M Schmidt-Supprian, M Rudelius, L Klein-Hitpass, AJ Finch, J Dürig…
Cancer cell, 2013cell.com
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 …
Summary
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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