Clonal expansion and not cell interconversion is the basis for the neuroblast and nonneuronal types of the SK-N-SH neuroblastoma cell line.
The ability of neuroblastoma (NB) cells to interconvert bidirectionally, in vitro, from a neuroblast (N) to a nonneuronal (S) form is a well-studied biologic phenomenon of great clinical importance. Differences in the morphologic/ biochemical characteristics and gene expression patterns of the two cell populations have been investigated extensively in an effort to unravel the transdifferentiation process. Subcloning of the SK-N-SH NB cell line has led to two morphologically distinct cell types: SH-SY5Y (N-type) and SH-EP (S-type). Karyotypic analysis combined with G-banding and SKY showed a difference between these two cell types in the copy number of the 2p15 approximately pter segment, including the MYC-N gene. FISH analysis showed an extra copy of MYC-N present in all three lines: in SK-N-SH and SH-SY5Y the majority of cells had three copies of MYC-N, whereas in SH-EP the majority had two copies and only a small cell population with three copies was present. We suggest that the simultaneous coexistence of both cell types and the subsequent clonal expansion of one over the other is a possible explanation for the phenomenon observed and not the accepted interconversion model. According to the clonal expansion model, both N and S cells are simultaneously present in both cell lines. Under certain conditions, the less-aggressive S cells can dominate over the highly aggressive N cells, which eventually lead to the formation of the SH-EP and vice-versa.
Department of Pediatric Hemato-Oncology and Institute of Hematology, The Chaim Sheba Medical Center, Tel Hashomer, Israel.
Ninette
N
Cohen
David R
DR
Betts
Gideon
G
Rechavi
Ninette
N
Amariglio
Luba
L
Trakhtenbrot
D002454:Cell Differentiation; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D002999:Clone Cells; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D009447:Neuroblastoma / Q000235:genetics / Q000473:pathology*; D014407:Tumor Cells, Cultured