DETECTION OF ACTIVATED PLATELET-DERIVED GROWTH-FACTOR RECEPTORS IN HUMAN MENINGIOMA

The beta receptor subunit of platelet-derived growth factor (PDGF) and its corresponding ligand (PDGF-BB) are coordinately expressed in fres h surgical isolates of human meningioma. These observations imply that PDGF autocrine loops are engaged in human meningioma and suggest that activated PDGF-beta receptors might contribute to the pathology of th is common brain neoplasm. The study of PDGF autocrine loops and human meningioma has been slowed by the scarcity of meningioma cell culture model systems. Furthermore, in meningioma tumor tissue, the activation state of PDGF receptors is difficult to assess with conventional reag ents, because the tumor is intermixed with normal stroma. In fact, the re is no evidence that PDGF receptors within the tumor are activated b y ligand. We used a synthetic tyrosine phosphopeptide to raise an anti body that reports the phosphorylation state of tyrosine 751 in the hum an PDGF-beta receptor. Phosphorylated tyrosine 751 is a recognition si te for phosphatidylinositol 3'-kinase, a cytoplasmic effector of PDGF- induced mitogenesis, chemotaxis, and membrane ruffling. Immunoblotting and immunostaining analyses with this antibody show that the PDGF-bet a receptor is constitutively phosphorylated at tyrosine 751 within mul tiple fresh surgical isolates of human meningioma. These findings are consistent with a role for activated PDGF receptors in the proliferati on of human meningiomas.