Control of meningioma cell growth by platelet-derived growth factor (PDGF).
We have examined the possible involvement of PDGF and PDGF receptors in the growth control of five meningiomas, analyzing the biopsy specimens and the primary cultures derived from the same tumors. Light and electron microscopy demonstrated that MAbs against PDGF beta-receptors immunodecorate meningioma cells in vivo and in vitro, while those against alpha-receptors gave negative results. The effects of PDGF isoforms AA, AB, BB and of PDGF neutralizing antibodies on meningioma cultures were examined using [3H]thymidine incorporation analysis. Only with PDGF-AB and -BB a mitogenic effect was observed, while PDGF-neutralizing antibodies produced a reduction of [3H]thymidine incorporation. The production of PDGF-like growth factors by meningioma cells was tested analyzing the effects of meningioma culture-conditioned media on the growth of Swiss 3T3 cells. In all cases meningioma conditioned media stimulated the in vitro growth of 3T3 fibroblasts and this stimulatory effect was strongly reduced by PDGF-neutralizing antibodies. Furthermore, Northern blot analysis demonstrated expression of c-sis/PDGF-B and PDGF beta-receptors mRNA in all meningioma biopsies and in all the derived cultures. Our results provide strong evidence that PDGF-B chain and PDGF beta-receptors are involved in growth control mechanisms of human meningiomas through autocrine and/or paracrine mechanisms.
Mauro
A
A
2nd Department of Neurology, University of Turin, Italy.
Di Sapio
A
A
Mocellini
C
C
Schiffer
D
D
D000911:Antibodies, Monoclonal; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D017077:Culture Media, Conditioned; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D008579:Meningioma / Q000473:pathology*; D016253:Microscopy, Immunoelectron; D009500:Neutralization Tests; D010982:Platelet-Derived Growth Factor / Q000276:immunology / Q000494:pharmacology*; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics / Q000276:immunology / Q000502:physiology; D013936:Thymidine; D014316:Tritium; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000648:ultrastructure
D000911:Antibodies, Monoclonal; D017077:Culture Media, Conditioned; D010982:Platelet-Derived Growth Factor; D014316:Tritium; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor; D013936:Thymidine