AUTOCRINE CONTROL OF HUMAN MENINGIOMA PROLIFERATION - SECRETION OF PLATELET-DERIVED GROWTH-FACTOR-LIKE MOLECULES

We have used cell-culture techniques to investigate growth-factor production by human meningioma cells. Meningioma tissue was dispersed with collagenase and the cells grown to high density in tissue-culture flasks. The cultures were used to generate conditioned medium (MEN-CM), which was used to cultivate IMR32 cells (a human neuroblastoma line) and freshly dispersed primary meningioma cells. MEN-CM profoundly stimulated the in vitro growth of both IMR32 and meningioma cells. In addition, H-3-thymidine uptake by cultured meningioma cells was increased in a dose-dependent manner by varying concentrations of MEN-CM. A neutralizing anti-body against platelet-derived growth factor (PDGF) completely abolished the stimulatory effects of MEN-CM, whereas an antibody against TGF-alpha was without effect. The mitogenic activity of MEN-CM, as assayed by promotion of H-3-thymidine uptake by cultured meningioma cells, eluted from a Sephadex G-100 column in 3 peaks corresponding to molecular weights of greater-than-or-equal-to 150, 56 and 28 kDa. Our results show that proliferation of human meningiomas may be under autocrine control via secretion of PDGF-like molecules.