TY  - JOUR
AU  - Pajtler, Kristian
AU  - Mahlow, Ellen
AU  - Odersky, Andrea
AU  - Lindner, Sven
AU  - Stephan, Harald
AU  - Bendix, Ivo
AU  - Eggert, Angelika
AU  - Schramm, Alexander
AU  - Schulte, Johannes
TI  - Neuroblastoma in dialog with its stroma: NTRK1 is a regulator of cellular cross-talk with Schwann cells.
JO  - OncoTarget
VL  - 5
IS  - 22
SN  - 1949-2553
CY  - [S.l.]
PB  - Impact Journals LLC
M1  - DKFZ-2017-00659
SP  - 11180 - 11192
PY  - 2014
AB  - 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.
KW  - Membrane Glycoproteins (NLM Chemicals)
KW  - Protein-Tyrosine Kinases (NLM Chemicals)
KW  - tropomyosin-related kinase-B, human (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:25361003
C2  - pmc:PMC4294349
DO  - DOI:10.18632/oncotarget.2611
UR  - https://inrepo02.dkfz.de/record/120072
ER  -