C17, a retrovirally immortalized neuronal cell line, inhibits the proliferation of astrocytes and astrocytoma cells by a contact‐mediated mechanism

Abstract

We have investigated the ability of various cell lines to effect contact-mediated inhibition of astrocytic cells. Of the lined tested, only C17, a mouse cell line from postnatal day 0 cerebellum immortalized by infection with a retroviral construct containing the avian myc gene, and U251, a human astrocytoma line, were able to inhibit the proliferation of astrocytic cells. With co-cultured with either primary astrocytes from rat cerebellum or the U251 line, the C17 cells induced a rapid cessaion of glial cell division as well as complex astrocytic process extension. The effects on glial mitosis were cell-dose-dependent, with ten C17 cells/glial cell being the optimal ratio. At this ratio [³H]thymidine incorporation into the U251 cells was reduced by greater than 80% and there was a virtual stasis in glial cell number at 48 hours. Fixed C17 cells as well as partially purified C17 membranes were also potent inhibitors of astrocytic proliferation, suggesting that the gliastatic effect of the C17 cell line is membrane associated. However, neither of these preparations induced astrocytic process formation. We also confirmed earlier reports that U251 cells inhibited their own proliferation in a density-dependent manner but at a lower fficiency than the C17 cells.