PMID- 19363525
OWN - NLM
STAT- MEDLINE
DCOM- 20090529
LR  - 20201222
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Linking)
VI  - 28
IP  - 19
DP  - 2009 May 14
TI  - Galectin-1 is a major effector of TrkB-mediated neuroblastoma aggressiveness.
PG  - 2015-23
LID - 10.1038/onc.2009.70 [doi]
AB  - Expression of Trk receptors is an important prognostic factor in neuroblastoma 
      (NB) and other cancers. TrkB and its ligand brain-derived neurotrophic factor 
      (BDNF) are preferentially expressed in NB with poor prognosis, conferring 
      invasive and metastatic potential to the tumor cells as well as enhancing therapy 
      resistance. Galectin-1 (Gal-1) has emerged as an interesting cancer target, as it 
      is involved in modulating cell proliferation, cell death and cell migration, all 
      of which are linked to cancer initiation and progression. We previously 
      identified Gal-1 mRNA to be upregulated in patients with aggressive, relapsing NB 
      and found that Gal-1 protein was upregulated in human SY5Y NB cells on activation 
      of ectopically expressed TrkB (SY5Y-TrkB), but not TrkA (SY5Y-TrkA). Here, we 
      report that Gal-1 mRNA levels positively correlated with TrkB expression and 
      anticorrelated with TrkA expression in a cohort of 102 primary NB. 
      Immunohistochemical analyses of 92 primary NB specimens revealed high Gal-1 
      expression in stromal septae and in neuroblasts. BDNF-mediated activation of TrkB 
      enhanced invasiveness and migration in vitro, which could be impaired by 
      transient transfection using Gal-1-specific siRNA or a neutralizing antibody 
      directed against Gal-1. The addition of recombinant Gal-1 (rGal-1) in the absence 
      of BDNF partially restored migration and invasive capacity. Using the Trk 
      inhibitor K252a, we could show that the upregulation of Gal-1 protein strictly 
      depended on activated TrkB. Our data suggest that targeting Gal-1 might be a 
      promising strategy for the treatment of aggressive NB.
FAU - Cimmino, F
AU  - Cimmino F
AD  - University Children's Hospital Essen, Germany.
FAU - Schulte, J H
AU  - Schulte JH
FAU - Zollo, M
AU  - Zollo M
FAU - Koster, J
AU  - Koster J
FAU - Versteeg, R
AU  - Versteeg R
FAU - Iolascon, A
AU  - Iolascon A
FAU - Eggert, A
AU  - Eggert A
FAU - Schramm, A
AU  - Schramm A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090413
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Galectin 1)
RN  - EC 2.7.10.1 (Receptor, trkA)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cell Line, Tumor
MH  - Cell Movement
MH  - Down-Regulation
MH  - Galectin 1/genetics/*metabolism
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Neuroblastoma/*physiopathology
MH  - Receptor, trkA/metabolism
MH  - Receptor, trkB/*metabolism
EDAT- 2009/04/14 09:00
MHDA- 2009/05/30 09:00
CRDT- 2009/04/14 09:00
PHST- 2009/04/14 09:00 [entrez]
PHST- 2009/04/14 09:00 [pubmed]
PHST- 2009/05/30 09:00 [medline]
AID - onc200970 [pii]
AID - 10.1038/onc.2009.70 [doi]
PST - ppublish
SO  - Oncogene. 2009 May 14;28(19):2015-23. doi: 10.1038/onc.2009.70. Epub 2009 Apr 13.