Demonstration of an activated platelet-derived growth factor autocrine pathway and its role in human tumor cell proliferation in vitro.
In tumor cells expressing platelet-derived growth factor (PDGF) ligand(s) and receptor(s), immunoblot analysis established tyrosine phosphorylation of PDGF receptors (PDGFRs) in the absence of any exogenous ligand, implying chronic receptor activation. Exposure to suramin resulted in diminished receptor autophosphorylation and/or up-regulation of receptor protein. In a subset of such tumor lines, there was a marked reduction in DNA synthesis in response to suramin or PDGF-neutralizing antiserum. These findings demonstrate that autocrine PDGF stimulation contributes to proliferation of some human tumors and that agents which interfere with ligand-receptor interactions at the cell surface can significantly interfere in this process.
Fleming
T P
TP
Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892.
Matsui
T
T
Heidaran
M A
MA
Molloy
C J
CJ
Artrip
J
J
Aaronson
S A
SA
D000906:Antibodies; D002455:Cell Division; D006801:Humans; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000378:metabolism / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000378:metabolism / Q000502:physiology*; D017479:Receptors, Platelet-Derived Growth Factor; D013498:Suramin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000906:Antibodies; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D013498:Suramin; D017479:Receptors, Platelet-Derived Growth Factor