CD57(high) neuroblastoma cells have aggressive attributes ex situ and an undifferentiated phenotype in patients.
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.


RESULTS
We investigated the role of CD57 expression in neuroblastoma cells ex situ and in situ. Compared to CD57(low) U-NB1 neuroblastoma cells, CD57(high) cells developed tumors with decreased latency after orthotopic transplantation into adrenal glands of mice. In addition, CD57(high) U-NB1 and SK-N-BE(2)-C neuroblastoma cells were also more clonogenic, induced more spheres and were less lineage-restricted. CD57(high) 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 CD57(high) cells generated liver metastases, while overall metastatic rate was not increased as compared to CD57(low) cells. In stroma-poor neuroblastoma of patients CD57(high) cells were associated with undifferentiated tumor cells across all stages and tended to be more frequent after chemotherapy.


CONCLUSIONS
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.
Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
Anne-Marie
AM
Schlitter
Carmen
C
Dorneburg
Thomas F E
TF
Barth
Joachim
J
Wahl
Johannes H
JH
Schulte
Silke
S
Brüderlein
Klaus-Michael
KM
Debatin
Christian
C
Beltinger
D000818:Animals; D018959:CD57 Antigens / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D019070:Cell Lineage / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D016130:Immunophenotyping; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000473:pathology / Q000556:secondary; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics; D009367:Neoplasm Staging; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D064531:Peripherins; D018874:Spheroids, Cellular; D014407:Tumor Cells, Cultured
D018959:CD57 Antigens; D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D064531:Peripherins