Sendai virus‐mediated expression of reprogramming factors promotes plasticity of human neuroblastoma cells

Neuroblastoma (NB) is the most common extracranial solid tumor that originates from multipotent neural crest cells. NB cell populations that express embryonic stem cell‐associated genes have been identified and shown to retain a multipotent phenotype. However, whether somatic reprogramming of NB cells can produce similar stem‐cell like populations is unknown. Here, we sought to reprogram NB cell lines using an integration‐free Sendai virus vector system. Of four NB cell lines examined, only SH‐IN cells formed induced pluripotent stem cell‐like colonies (SH‐IN 4F colonies) at approximately 6 weeks following transduction. These SH‐IN 4F colonies were alkaline phosphatase‐positive. Array comparative genomic hybridization analysis indicated identical genomic aberrations in the SH‐IN 4F cells as in the parental cells. SH‐IN 4F cells had the ability to differentiate into the three embryonic germ layers in vitro, but rather formed NBs in vivo. Furthermore, SH‐IN 4F cells exhibited resistance to cisplatin treatment and differentiated into endothelial‐like cells expressing CD31 in the presence of vascular endothelial growth factor. These results suggest that SH‐IN 4F cells are partially reprogrammed NB cells, and could be a suitable model for investigating the plasticity of aggressive tumors. Multipotent neuroblastoma cell populations express embryonic stem cell‐associated genes and contribute to the aggresiveness of neuroblastomas; however it has never been examined whether somatic reprogramming of neuroblastoma cells could produce the stem‐cell like populations. In this study, we transduced reprogramming factors in SH‐IN neuroblastoma cells using an integration‐free Sendai virus vector system and found that the reprogrammed SH‐IN cells show resistance to cisplatin treatment and differentiate into endothelial‐like cells expressing CD31 in the presence of vascular endothelial growth factor.