Tumor Biology

, Volume 31, Issue 2, pp 121–128

Brain-derived neurotrophic factor induces proliferation, migration, and VEGF secretion in human multiple myeloma cells via activation of MEK-ERK and PI3K/AKT signaling

  • Chun-yan Sun
  • Yu Hu
  • Jing Huang
  • Zhang-bo Chu
  • Lu Zhang
  • Xiao-mei She
  • Lei Chen
Article

DOI: 10.1007/s13277-010-0016-x

Cite this article as:
Sun, C., Hu, Y., Huang, J. et al. Tumor Biol. (2010) 31: 121. doi:10.1007/s13277-010-0016-x
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Abstract

This study investigated the signaling pathways involved in the different biological effects of brain-derived neurotrophic factor (BDNF) in multiple myeloma (MM). The effects of BDNF on proliferation of MM cell lines and primary myeloma cells were examined by [3H]thymidine incorporation assay. The effects of BDNF on MM cells migration were studied by transwell migration assay. Stimulation by BDNF of vascular endothelial growth factor (VEGF) production was analyzed by reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay. The signal-transduction pathways that are activated in response to BDNF were determined by Western blots. VEGF is induced by BDNF in a dose-dependent manner in MM cells. Stimulation of MM cells with BDNF led to the activation of the phosphatidylinositol 3-kinase (PI3K)/Akt and the MEK-extracellular signal-regulated protein kinase pathways. Using specific signal-transduction inhibitors, we demonstrated that MEK is required for BDNF-induced proliferation, whereas activation of PI3K is required for BDNF-stimulated migration and VEGF production. BDNF affects different cell signaling pathways mediating growth, migration, and VEGF secretion in MM cells. Our observations provided the framework for novel therapeutic strategies targeting BDNF signaling cascades in MM.

Keywords

Multiple myeloma Brain-derived neurotrophic factor Proliferation Migration Vascular endothelial growth factor Signal transduction 

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2010

Authors and Affiliations

  • Chun-yan Sun
    • 1
  • Yu Hu
    • 1
  • Jing Huang
    • 1
  • Zhang-bo Chu
    • 1
  • Lu Zhang
    • 1
  • Xiao-mei She
    • 1
  • Lei Chen
    • 1
  1. 1.Institute of Hematology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanPeople’s Republic of China

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