Autocrine NGFbeta/TRKA signalling is an important survival factor for Hodgkin lymphoma derived cell lines

Leuk Res. 2008 Jan;32(1):163-7. doi: 10.1016/j.leukres.2007.05.019. Epub 2007 Jul 27.

Abstract

Hodgkin-Reed/Sternberg cells, the tumor cells of Hodgkin lymphoma, aberrantly express several receptor tyrosine kinases, among them TRKA whose stimulation supports B cell survival. We show here high expression of TRKA in Hodgkin-Reed/Sternberg cell lines as compared to normal B cells and other B cell lymphomas, without major increases in TRKA gene dosage. A fraction of TRKA is constitutively activated, likely due to the coexpression of NGFbeta, the TRKA high affinity ligand. The TRK inhibitor K-252a decreased survival of Hodgkin-Reed/Sternberg cell lines accompanied by decreased AKT activation. Inclusion of TRK inhibitors in therapeutic regimens may thus be an interesting possibility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes
  • Carbazoles / pharmacology
  • Cell Line, Tumor
  • Hodgkin Disease
  • Humans
  • In Situ Hybridization, Fluorescence
  • Indole Alkaloids / pharmacology
  • Nerve Growth Factor / metabolism*
  • Receptor, trkA / antagonists & inhibitors
  • Receptor, trkA / metabolism*
  • Signal Transduction

Substances

  • Carbazoles
  • Indole Alkaloids
  • NGF protein, human
  • Nerve Growth Factor
  • staurosporine aglycone
  • Receptor, trkA