Microglia-derived cytotoxic factors. Part I: Inhibition of tumor cell growth in vitro

The rarity of neoplasms in the adult mammalian retina has led us to hypothesize the presence or increased expression of 'tumor-inhibitory molecules' in the mature differentiated retina. We have begun to investigate the source(s) of these molecules, and the following study describes the inhibitory activity of a soluble microglia-derived cytotoxic factor on the proliferation of C6 cells, a glial tumor cell line. C6 cells were treated for 24, 48, or 72 h with basal medium or basal medium conditioned by retina-derived Muller cells (MCCM) or microglial cells (MGCM) and assayed for cell proliferation and/or cell death using various techniques involving fluorescent probes, lactate dehydrogenase release, or bromodeoxyuridine uptake. C6 cells increased in number from 24 to 72 h following incubation in basal medium or MCCM, but not in MGCM, where the cells rounded up and retracted their processes. The number of dead cells appeared to be the same in all groups at each time point. Similar findings were observed in the presence of 1-10% serum. About 25% of cells treated with basal medium for 72 h were positive for bromodeoxyuridine as compared with < 1% in MGCM-treated cultures. Our studies suggest that retina-derived microglial cells secrete soluble product(s) that inhibit the growth of C6 cells in culture. These molecules may provide protection for the mature retina against the invasion of tumor cells and may prove useful in the treatment of cancer.