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@ARTICLE{Pajtler:120072,
author = {K. Pajtler$^*$ and E. Mahlow and A. Odersky and S. Lindner
and H. Stephan and I. Bendix and A. Eggert and A. Schramm
and J. Schulte$^*$},
title = {{N}euroblastoma in dialog with its stroma: {NTRK}1 is a
regulator of cellular cross-talk with {S}chwann cells.},
journal = {OncoTarget},
volume = {5},
number = {22},
issn = {1949-2553},
address = {[S.l.]},
publisher = {Impact Journals LLC},
reportid = {DKFZ-2017-00659},
pages = {11180 - 11192},
year = {2014},
abstract = {In neuroblastoma, the most common solid tumor of childhood,
excellent prognosis is associated with extensive Schwann
cell (SC) content and high-level expression of the
neurotrophin receptor, NTRK1/TrkA, which is known to mediate
neuroblastoma cell differentiation. We hypothesized that
both stromal composition and neuroblastic differentiation
are based on bidirectional neuroblastoma-SC interaction.
Reanalysis of microarray data from human SY5Y neuroblastoma
cells stably transfected with either NTRK1 or NTRK2 revealed
upregulation of the mRNA for the SC growth factor, NRG1, in
NTRK1-positive cells. Media conditioned by NTRK1-expressing
neuroblastoma cells induced SC proliferation and migration,
while antibody-based NRG1 neutralization significantly
decreased these effects. Vice versa, NRG1-stimulated SC
secreted the NTRK1-specific ligand, NGF. SC-conditioned
medium activated the NTRK1 receptor in a neuroblastoma cell
culture model conditionally expressing NTRK1 and induced
differentiation markers in NTRK1-expressing cells. NTRK1
induction in neuroblastoma xenografts mixed with primary SC
also significantly reduced tumor growth in vivo. We propose
a model for NTRK1-mediated and NRG1-dependent attraction of
adjacent SC, which in turn induce neuroblastic
differentiation by secretion of the NTRK1-specific ligand,
NGF. These findings have implications for understanding the
mature and less malignant neuroblastoma phenotype associated
with NTRK1 expression, and could assist the development of
new therapeutic strategies for neuroblastoma
differentiation.},
keywords = {Membrane Glycoproteins (NLM Chemicals) / Protein-Tyrosine
Kinases (NLM Chemicals) / tropomyosin-related kinase-B,
human (NLM Chemicals)},
cin = {B062 / L401},
ddc = {610},
cid = {I:(DE-He78)B062-20160331 / I:(DE-He78)L401-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:25361003},
pmc = {pmc:PMC4294349},
doi = {10.18632/oncotarget.2611},
url = {https://inrepo02.dkfz.de/record/120072},
}