CD57high Neuroblastoma cells have aggressive attributes Ex situ and an undifferentiated phenotype in patients

Abstract

Background: Neuroblastoma is thought to originate from neural crest-derived cells. CD57 defines migratory neural crest cells in normal development and is expressed in neuroblastoma. Methodology and Principal Findings: We investigated the role of CD57 expression in neuroblastoma cells ex situ and in situ. Compared to CD57low U-NB1 neuroblastoma cells, CD57high cells developed tumors with decreased latency after orthotopic transplantation into adrenal glands of mice. In addition, CD57high U-NB1 and SK-N-BE(2)-C neuroblastoma cells were also more clonogenic, induced more spheres and were less lineage-restricted. CD57high cells attached better to endothelial cells and showed enhanced invasiveness. While invasion of U-NB1 cells was inhibited by blocking antibodies against CD57, neither invasion of SK-N-BE(2)-C cells nor adhesion of U-NB1 and SK-N-BE(2)-C cells was attenuated. After tail vein injection only CD57high cells generated liver metastases, while overall metastatic rate was not increased as compared to CD57low cells. In stroma-poor neuroblastoma of patients CD57high cells were associated with undifferentiated tumor cells across all stages and tended to be more frequent after chemotherapy. Conclusion: Strong expression of CD57 correlates with aggressive attributes of U-NB1 and SK-N-BE(2)-C neuroblastoma cells and is linked with undifferentiated neuroblastoma cells in patients. © 2012 Schlitter et al.