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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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

Associated data

  • GEO/GSE36416