A neurotrophin axis in myeloma: TrkB and BDNF promote tumor-cell survival. Academic Article uri icon

Overview

MeSH

  • Autocrine Communication
  • Boronic Acids
  • Bortezomib
  • Cell Line, Tumor
  • Cell Survival
  • Coculture Techniques
  • Dexamethasone
  • Humans
  • Paracrine Communication
  • Pyrazines
  • Signal Transduction
  • Stromal Cells

MeSH Major

  • Brain-Derived Neurotrophic Factor
  • Multiple Myeloma
  • Nerve Growth Factors
  • Receptor, trkB

abstract

  • Multiple myeloma (MM) is a B-cell neoplasm that is characterized by the clonal expansion of malignant plasma cells and is frequently associated with chromosomal translocations placing an oncogene under the control of the immunoglobulin heavy chain enhancer. Despite these pathogenic translocations, MM cells remain dependent on external cues for survival. We present evidence that brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family of growth factors, and its high-affinity receptor, tropomyosin receptor kinase B (TrkB), contribute to these survival cues. MM cells express TrkB, and respond to BDNF by activating mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3 kinase-a PI3K target (PI3K/Akt) signaling cascades. Addition of BDNF protects human MM cell lines (HMCLs) from apoptosis induced by dexamethasone or bortezomib and prolongs the survival of primary MM cells cultured alone or with human bone marrow (BM) stroma. As BDNF and TrkB are expressed by osteoblasts, stromal cells, and endothelial cells within the BM microenvironment, a BDNF-TrkB axis may be critical to the interactions of MM with bone and stroma that contribute to MM tumor progression. Finally, BDNF is expressed by malignant plasma cells isolated from a subset of patients with MM, as well as by most HMCLs, suggesting a potential role for this neurotrophin axis in autocrine as well as paracrine support of MM.

publication date

  • June 1, 2005

has subject area

  • Autocrine Communication
  • Boronic Acids
  • Bortezomib
  • Brain-Derived Neurotrophic Factor
  • Cell Line, Tumor
  • Cell Survival
  • Coculture Techniques
  • Dexamethasone
  • Humans
  • Multiple Myeloma
  • Nerve Growth Factors
  • Paracrine Communication
  • Pyrazines
  • Receptor, trkB
  • Signal Transduction
  • Stromal Cells

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1182/blood-2004-08-3096

PubMed ID

  • 15657181

Additional Document Info

start page

  • 4429

end page

  • 4436

volume

  • 105

number

  • 11