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 fresh 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 this 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 reagents, because the tumor is intermixed with normal stroma. In fact, there is no evidence that PDGF receptors within the tumor are activated by ligand. We used a synthetic tyrosine phosphopeptide to raise an antibody that reports the phosphorylation state of tyrosine 751 in the human PDGF-beta receptor. Phosphorylated tyrosine 751 is a recognition site 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-beta receptor is constitutively phosphorylated at tyrosine 751 within multiple fresh surgical isolates of human meningioma. These findings are consistent with a role for activated PDGF receptors in the proliferation of human meningiomas.
Shamah
S M
SM
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Alberta
J A
JA
Giannobile
W V
WV
Guha
A
A
Kwon
Y K
YK
Carroll
R S
RS
Black
P M
PM
Stiles
C D
CD
D016475:3T3 Cells; D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology*; D000918:Antibody Specificity; D001921:Brain / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D007158:Immunologic Techniques; D008579:Meningioma / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D019000:Phosphotyrosine / Q000276:immunology*; D020794:Receptor Protein-Tyrosine Kinases / Q000276:immunology / Q000378:metabolism*; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor / Q000276:immunology / Q000378:metabolism*
D000912:Antibodies, Neoplasm; D019000:Phosphotyrosine; D020794:Receptor Protein-Tyrosine Kinases; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor