ENHANCED TOLERANCE OF NEUROBLASTOMA-CELLS TOWARDS THE NEUROTOXIN 6-HYDROXYDOPAMINE FOLLOWING SPECIFIC CELL-CELL INTERACTION WITH PRIMARY ASTROCYTES

Dopamine neuroblastoma (SH-SY5Y) cells exhibit a high affinity of adhe sion for primary astroglial cells. The hemophilic aggregation of SH-SY 5Y cells is greatly reduced and the neuroprocesses are enhanced when c o-cultured with the astrocytes. However, such affinity was not detecte d in the mouse when these cells were co-cultured with fibroblast and e ndothelial cells. SH-SY5Y cells in monoculture are very sensitive towa rds the neurotoxin B-hydroxydopamine, but this sensitivity is substant ially reduced in co-culture with astrocytes. The acquired cytoprotecti on of the neuroblastoma cells in co-culture against 6-hydroxydopamine is rime dependent following adhesion with the astrocytes. There is no evidence to indicate that the increase in survival of the SH-SY5Y cell s against 6-hydroxydopamine is due to inactivation of B-hydroxydopamin e induced by the extracellular factors secreted from the astrocytes, n either is there any indication suggesting the removal of 6-hpdroxydopa mine by an astrocyte uptake mechanism. The release of trophic factors by the astrocytes does not seem to play a role in the protection of th e neuroblastoma cells against 6-hydroxydopamine. The neuroblastoma cel ls became susceptible to 6-hydroxydopamine in the astrocyte co-culture s when they were physically separated from the astroglial cells by tra ns-well inserts. Neither non-selective adhesions, such as adhesion wit h denatured astrocytes or with other types of cells (i.e. endothelial or fibroblast cells), nor adhesion enhanced by chemical agents can inc rease the cytoprotection of SH-SY5Y against 6-hydroxydopamine. These r esults suggest that the increase in survival of neuroblastoma cells ag ainst 6-hydroxydopamine in the astrocyte co-cultures is probably a res ult of specific cell-cell adhesion and the subsequent interactions. (C ) 1997 IBRO.