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.