Neuroblastoma is the most common solid tumor in infancy and the high-risk form has still a dismal outcome although multimodal treatment. MYCN amplification is a negative prognostic marker and contributes to maintain an undifferentiated phenotype of neuroblastoma. The overall aim of this study is to explore regulatory pathways of controlling differentiation of neuroblastoma cells and the potential of activating these pathways as a mode of action of therapy.
We found that p75NTR, a cell surface receptor that gets internalized upon ligand binding, is regulated by estrogen signaling. Thus, the aim of this study was to further investigate the role of the receptor in differentiation of NB cells. Interestingly, p75NTR was mainly located perinuclear in NB cells overexpressing ERα. Activation of ERα resulted in upregulation of p75NTR and redistribution throughout the cytoplasm, whereas control cells remained unaffected by the estradiol treatment. A more detailed analysis showed that p75NTR was located at the microtubule-organizing center (MTOC) and the golgi at low concentrations, whereas it was detected in vesicles at high expression levels. p75NTR can regulate the depolymerization of actin through inhibition of Rho-GTPases. Since Rho-GTPases are important players during the organization of the cytoskeleton in neuronal cells, we analyzed if p75NTR is involved in the cytoskeletal rearrangements during differentiation. Temporary disruption of the microtubules using nocodazole resulted in a dispersion of p75NTR in the cytoplasm. After nocodazole removal, a rapid localization of p75NTR to the center from where the microtubules regenerated was observed and the original structure was restored.
Here we identified a putative role of p75NTR during the regulation of the cytoskeleton in neuronal differentiation of neuroblastoma cells. Further studies will be needed to elucidate the role of p75NTR in neuronal differentiation of neuroblastoma cells.