Inhibition of platelet-derived growth factor autocrine growth stimulation by a monoclonal antibody to the human alpha platelet-derived growth factor receptor.
A potent neutralizing monoclonal antibody to the human alpha platelet-derived growth factor (PDGF) receptor (alpha PDGFR) was raised by immunizing BALB/c mice with 32D cells expressing the human alpha PDGFR. This monoclonal antibody, designated alpha R1, immunoprecipitated human, monkey, rabbit, pig, dog, and cat, but not hamster, rat, or mouse alpha PDGFRs. Comparison with PR292, a monoclonal antibody previously generated against the alpha PDGFR, showed that both recognized alpha PDGFR extracellular domains, but neither demonstrated reactivity against the beta PDGFR. In vitro binding studies revealed that alpha R1, but not PR292, detection of the alpha PDGFR was blocked by either PDGF AA or PDGF BB. These results strongly suggest that the receptor ligand-binding domain spatially overlapped with the alpha R1 epitope. Monoclonal antibody alpha R1 also inhibited PDGF stimulation of [3H]thymidine uptake by 32D cells expressing the alpha PDGFR (32D alpha R) as well as autocrine growth stimulation of 32D alpha R cells transfected with and expressing PDGF AA or PDGF BB. Therefore, monoclonal antibody alpha R1 may be useful in the detection and growth inhibition of malignancies in which PDGF autocrine stimulation and/or alpha PDGFR overexpression plays an important role(s).
LaRochelle
W J
WJ
Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892.
Jensen
R A
RA
Heidaran
M A
MA
May-Siroff
M
M
Wang
L M
LM
Aaronson
S A
SA
Pierce
J H
JH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis*; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D002415:Cats; D002455:Cell Division / Q000235:genetics; D006224:Cricetinae; D004285:Dogs; D000939:Epitopes; D000882:Haplorhini; D006728:Hormones / Q000276:immunology*; D006801:Humans; D007120:Immunochemistry; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000276:immunology*; D011817:Rabbits; D051381:Rats; D017479:Receptors, Platelet-Derived Growth Factor / Q000276:immunology*; D013552:Swine; D014162:Transfection; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000939:Epitopes; D006728:Hormones; D010982:Platelet-Derived Growth Factor; D017479:Receptors, Platelet-Derived Growth Factor