Morphological and biochemical differentiation of the human medulloblastoma cell line TE671

Cells of the human medulloblastoma clonal line TE671 exhibit polymorphism when grown in vitro in serum-supplemented medium. Under these conditions, cell numbers double every 18 h during log phase growth. These tumorigenic precursors of cerebellar interneurons are not contact-inhibited and approach densities of one million cells per cm2. TE671 cells in proliferative growth express a class of nicotinic acetylcholine receptors that are fully sensitive to functional blockade by the neurotoxin alpha-bungarotoxin (Bgt). TE671 cells grown in medium containing dibutyryl cyclic adenosine monophosphate (dbcAMP) rapidly undergo a distinctive morphological transformation characterized by neurite extension and formation of cell-cell contacts. The rate of cell division and cell saturation densities are diminished coordinately with these treatments. Sodium fluoride and forskolin induce similar changes in cell division and morphology as does dbcAMP, and these effects are potentiated by aluminum and the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, respectively. The high-affinity binding of Bgt to TE671 cells also is reduced on exposure to dbcAMP in a time and dose-dependent manner. The results suggest that activation of adenylate cyclase and the concomitant elevation of intracellular cAMP levels may be involved in the morphological transformation of TE671 cells to a mature, neuronal phenotype and in changes in the level of expression of a subtype of human neuronal nicotinic receptors. These studies establish a unique, neural tube-derived model system for investigation of the mechanisms involved in these processes.