Human neuroblastoma cell line SNU-NB1 loses sensitivity to brain-derived neurotrophic factor during establishment

Background and aims: The expression pattern of high affinity neurotrophin receptors dichotomizes the clinicopathologic characteristics of neuroblastoma (NB). The effects mediated by trkA have been documented in many experimental systems, whereas the effects mediated by trkB have only been investigated in limited studies. Methods: We established a new cell line of NB, “SNU-NB1”, by primary culture and the effects mediated by trkB were addressed in this cell line. Results: NB cells in primary culture showed amplification of N-myc and expression of trkB. Activation of trkB in primary culture by brain-derived neurotrophic factor (BDNF) was followed by activation of extracellular signal-regulated kinase1/2 (ERK1/2), growth inhibition, neuronal differentiation, and N-myc down-regulation. However, fully transformed SNU-NB1 cells lost BDNF sensitivity while being tumorigenic in vivo. Restoration of trkB expression in SNU-NB1 cells, by retroviral infection of trkB, induced differentiation and inhibition of growth in the cells following BDNF treatment. Although the prognosis of neuroblastomas is different according to the status of trkA and trkB mRNA expressions, the cytologic effects mediated by trkB per se are similar to those by trkA in NB. Conclusion: The patterns of trkA and trkB mRNA expression were markers for different lineages of transformed cells but were inconsistent with the clinical behavior.