Neurotrophin effects on neuroblastoma cells: correlation with Trk and p75NTR expression and influence of Trk receptor bodies

Neurotrophins are key signalling molecules in the development of the nervous system. They elicit diverse cellular responses such as proliferation, differentiation, survival and apoptosis. Neurotrophins (NTs) bind to two different classes of cell surface receptors, Trk receptor tyrosine kinases and p...

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Bibliographic Details
Published in:Journal of neuro-oncology 2004, Vol.66 (1-2), p.101-110
Main Authors: EVANGELOPOULOS, M. E, WEIS, J, KRUTTGEN, A
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cell Division - drug effects
Cell Line, Tumor
Cell Survival - drug effects
Humans
Medical sciences
Mice
Nerve Growth Factors - pharmacology
Neuroblastoma - metabolism
Neuroblastoma - pathology
Neurology
Receptor, Nerve Growth Factor
Receptor, trkA - genetics
Receptor, trkA - metabolism
Receptor, trkB - genetics
Receptor, trkC - genetics
Receptors, Fc - genetics
Receptors, Nerve Growth Factor - metabolism
Recombinant Fusion Proteins - metabolism
Recombinant Proteins - pharmacology
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Summary:Neurotrophins are key signalling molecules in the development of the nervous system. They elicit diverse cellular responses such as proliferation, differentiation, survival and apoptosis. Neurotrophins (NTs) bind to two different classes of cell surface receptors, Trk receptor tyrosine kinases and p75NTR, both of which are expressed by neuroblastoma cells. Neurotrophin signalling via Trks was shown to promote both survival and differentiation of neuroblastoma cells in vitro. The expression of certain Trk receptors is considered to be a prognostic indicator. The p75NTR receptor is the founding member of the Fas/TNF-R family, which is best known for its function in the induction of apoptosis. Its function in neuroblastomas is thus far poorly understood. We analysed neurotrophin receptor (NTR) expression of neuroblastoma cells by surface biotinylation assays and applied recombinant nerve growth factor (NGF), brain-derived neurotrophic factor, neurotrophin-3 and neurotrophin-4/5 to these cell lines assessing their survival and proliferation in long-term assays lasting 6 days. NGF increased proliferation of Neuro 2a cells, which express p75NTR but no TrkA receptors on their surface. On the other hand, SK-N-BE cell proliferation was decreased after NGF treatment, even though these cells also express p75NTR but no TrkA receptors on their surface. Interestingly, neurotrophin-scavenger proteins (TrkB-Fc and TrkC-Fc) as well as chemical blockers of Trk receptor signalling (K252a, Wortmannin, PD98059) slowed down the proliferation of both cell lines in medium containing serum. Taken together, our results indicate that p75NTR activation has diverse effects on neuroblastomas, depending on the specific neuroblastoma clone. In addition, our studies point towards TrkB-Fc or TrkC-Fc receptor bodies as useful tools to influence the survival of neuroblastoma cells.
ISSN:0167-594X
1573-7373
DOI:10.1023/B:NEON.0000013492.37426.0c