Journal of Neuroscience, Vol 8, 1447-1453, Copyright © 1988 by Society for Neuroscience
Mouse cerebellar granule neurons arrest the proliferation of human and rodent astrocytoma cells in vitro
ME Hatten and ML Shelanski
Department of Pharmacology, New York University School of Medicine, New York 10016.
To understand the control of glial tumor cell proliferation, we have
examined the effects of neurons on a number of human and rodent glioma
lines. These included C6, G26-24, U-251, HTB-16, and A-172 cells of
astroglial lineage and G26-20 of bipotential astrocytic and
oligodendrocytic lineage. Rapid, specific binding of granule neurons to the
human A-172, HTB-16, and U-251 and mouse G26-24 cell lines occurred, after
which 3H-thymidine incorporation by these astrocytoma cells dropped
2-5-fold within 12 hr. The number of glial cells remained constant for 5-7
d when the glia were cocultured with granule neurons. Thereafter many
neurons detached from the glial cells and glial proliferation commenced
again. No effects on glial cell number were seen when PC12 cells were
substituted for cerebellar granule neurons. To test the mechanism of
neuronal control of glioma cell growth, we added granule neurons or PC12
cells that had been fixed lightly with paraformaldehyde, a plasma membrane
fraction of purified granule cells, PC12 cells or astrocytoma cells, or
medium conditioned by either granule cells or a mixed population of
cerebellar neurons and astroglia. The proliferation of responsive glioma
cell lines ceased in the presence of either fixed granule neurons or plasma
membranes purified from granule neurons. The addition of fixed PC12 cells
or plasma membranes purified from PC12 cells, 3T3 cells, or astrocytoma
cells had no effect on glial cell growth.(ABSTRACT TRUNCATED AT 250 WORDS)