Autocrine growth stimulation of human meningioma cells by platelet-derived growth factor.

The authors have previously shown that meningioma-derived conditioned medium profoundly stimulates the in vitro proliferation of meningioma cells. In this paper, self mitogenic agents found in the conditioned medium-autocrine growth-stimulatory factors actually secreted by human meningioma cells-are characterized as proteins related to the B chain of platelet-derived growth factor (PDGF) and possibly to the A chain of PDGF as well. The addition to conditioned medium of a neutralizing antibody against PDGF-BB caused a significant inhibition of the conditioned medium-stimulated DNA synthesis in all three meningioma cultures studied. A similar neutralizing effect was observed with an anti-PDGF-AA antibody in one meningioma culture studied. Gel filtration chromatography of concentrated conditioned medium from two different meningiomas using a Sephadex G-100 column revealed similar profiles from both conditioned media with a major peak of mitogenic activity against meningioma cells at a molecular weight (M(r)) of approximately 32 to 36 kD, accompanied by a minor peak at approximately 22 kD. The major peak mitogenic activity was significantly reduced by addition of an anti-PDGF-BB antibody. Western blot analysis of protein extracts from five meningioma specimens was performed using a monoclonal antibody against the B chain of PGDF, and a major band of PDGF-B immunoreactivity was detected at an M(r) of approximately 19 kD in all five meningiomas under both reducing and nonreducing conditions. Exogenous human and porcine PDGFs both exhibited a significant dose-dependent stimulation of DNA synthesis in two of three and three of five meningioma cultures examined, respectively. Although not all meningiomas investigated proved to share the biological activity associated with PDGF and these results may be preliminary, it seems that the autocrine growth-stimulatory loop established by PDGF-B-related molecules plays an important functional role in meningioma cell proliferation.