Receptors for platelet derived growth factor in human glioma cell lines and influence of suramin on cell proliferation.
A panel of 11 established human glioma cell lines was used to evaluate PDGF receptor binding using radioiodinated biosynthetic PDGF-AA and PDGF-AB as primary ligands. It was found that PDGF-receptor-binding was qualitatively heterogeneous. The affinities for PDGF-AA as well as PDGF-AB binding were within a close range of 0.13-0.33 nM and 0.16-1.1 nM, respectively. The number of binding sites per cell ranged between 56.000 and 250.000 for PDGF-AA and 72.000 to 300.000 for PDGF-AB. Two lines had only background levels of PDGF-AA binding. PDGF-AB binding was the dominant binding component in all but one cell line. In seven cell lines there were two binding components upon saturation analysis consisting of a high affinity component and a non-saturable low affinity component. PDGF and PDGF-receptors are suspected to be part of an autocrine loop in gliomas. Therefore, the effect of suramin on cell proliferation in serumfree cultures was tested in the same cell lines using doses of 25,200 or 500 micrograms/ml. It was found that the response to suramin was variable and that two cell lines still reached 2.8 fold and 4.5 fold their initial cell density even in the presence of 500 micrograms/ml whereas all other cells were completely arrested. Analyzing the response to 200 micrograms/ml it became evident, that the PDGF binding characteristics are of no reliable predictive value in respect to the efficacy of suramin.
Westphal
M
M
Department of Neurosurgery, University Hospital Eppendorf, Hamburg, Germany.
Ackermann
E
E
Hoppe
J
J
Herrmann
H D
HD
D001932:Brain Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D005910:Glioma / Q000473:pathology*; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor; D011994:Recombinant Proteins / Q000378:metabolism; D013498:Suramin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D009363:Neoplasm Proteins; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D013498:Suramin; D017479:Receptors, Platelet-Derived Growth Factor