Factors released by rat type 1 astrocytes exert different effects on the proliferation of human neuroblastoma cells (SH-SY5Y) in vitro

Brain metastases derived from abdominal neuroblastoma are an uncommon compl ication of this tumour; however, an increase in their occurrence has recent ly been reported. In the present study, we have investigated the influence of factors derived from central nervous system glial cells on the prolifera tion of human neuroblastoma cells (SH-SY5Y) in vitro. Go-culture experiment s show that a 24-h exposure to factors released by type 1 astrocytes (Al) m ay induce a significant decrease in [H-3]thymidine ([H-3]TdR) incorporation by SH-SY5Y cells. This effect was not duplicated by fresh A1-conditioned m edium (AI-CM); AI-CM became active only when it was heated or frozen. In co ntrast to this short-lived inhibitory effect, long-term treatment (3, 6 and 9 days) with A1-CM produced a significant and dose-dependent increase in S H-SY5Y cell number. Immunoneutralisation of Al-CM with an anti-transforming growth factor-beta antibody eliminated the inhibitory effect on [H-3]TdR u ptake in SH-SY5Y cells, but did not affect the increased number of viable c ells observed after long-term treatments, In conclusion, these results showed that factor(s) released by Al may affec t the proliferation/survival of a human neuroblastoma cell line in vitro in ducing: (a) a short transient negative effect on DNA synthesis and (b) an o verall sustained trophic action. These results are suggestive of a possible role of glial cells in the establishment of brain metastases of neuroblast omas.