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Neuroscience. 1997 Jun;78(3):903-12.

Enhanced tolerance of neuroblastoma cells towards the neurotoxin 6-hydroxydopamine following specific cell-cell interaction with primary astrocytes.

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Department of Psychiatry, University of Saskatchewan, Saskatoon, Canada.


Dopamine neuroblastoma (SH-SY5Y) cells exhibit a high affinity of adhesion for primary astroglial cells. The homophilic aggregation of SH-SY5Y cells is greatly reduced and the neuroprocesses are enhanced when co-cultured with the astrocytes. However, such affinity was not detected in the mouse when these cells were co-cultured with fibroblast and endothelial cells. SH-SY5Y cells in monoculture are very sensitive towards the neurotoxin 6-hydroxydopamine, but this sensitivity is substantially reduced in co-culture with astrocytes. The acquired cytoprotection of the neuroblastoma cells in co-culture against 6-hydroxydopamine is time dependent following adhesion with the astrocytes. There is no evidence to indicate that the increase in survival of the SH-SY5Y cells against 6-hydroxydopamine is due to inactivation of 6-hydroxydopamine induced by the extracellular factors secreted from the astrocytes, neither is there any indication suggesting the removal of 6-hydroxydopamine by an astrocyte uptake mechanism. The release of trophic factors by the astrocytes does not seem to play a role in the protection of the neuroblastoma cells against 6-hydroxydopamine. The neuroblastoma cells became susceptible to 6-hydroxydopamine in the astrocyte co-cultures when they were physically separated from the astroglial cells by trans-well inserts. Neither non-selective adhesions, such as adhesion with denatured astrocytes or with other types of cells (i.e. endothelial or fibroblast cells), nor adhesion enhanced by chemical agents can increase the cytoprotection of SH-SY5Y against 6-hydroxydopamine. These results suggest that the increase in survival of neuroblastoma cells against 6-hydroxydopamine in the astrocyte co-cultures is probably a result of specific cell-cell adhesion and the subsequent interactions.

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