Regulation of DNA synthesis and growth of cells derived from primary human meningiomas.

We have studied the effects of insulin, epidermal growth factor (EGF), fibroblast growth factor (FGF), platelet-derived growth factor, and steroid hormones (estradiol, progesterone, and cortisol) on human meningioma cell proliferation and DNA synthesis in a serum-free culture system. The growth factors, particularly EGF and FGF, increased DNA synthesis in a dose-dependent manner as measured by [3H]thymidine incorporation, and they stimulated submaximal cell proliferation. No individual factor or combination of factors was able to successfully reproduce the effects of 10% fetal calf serum (FCS) on cell growth, although a combination of platelet-derived growth factor (5 units/ml) and EGF (10 ng/ml) synergistically stimulated DNA synthesis to near maximal levels. In addition, serum dependency was observed in studies involving the mitogenic effects of insulin, EGF, or FGF. Both EGF and FGF (10 ng/ml) maximally stimulated cell growth in the presence of 5% FCS. The effects of steroid hormones on cell proliferation, individually or in combination with growth factors or charcoal-treated FCS, were also evaluated. Estradiol (100 nM) significantly increased cell number over control values only in the presence of charcoal-treated FCS; no effects of progesterone or cortisol on cell proliferation were observed. In conclusion, both EGF and FGF stimulated cell proliferation and DNA synthesis in human meningioma cultures in a serum-free system, whereas steroid hormones were without effect. It appears that additional serum components are required for both estradiol-stimulated growth and for maximal proliferation of human meningioma cells under serum-free conditions.