title: Biphasic effects of suramin on 125I-epidermal growth factor binding to human meningiomas.
abstract: 1. We studied the effects of suramin, a nonspecific growth factor antagonist, on epidermal growth factor (EGF) binding to cell surface receptors in surgically excised human meningiomas, using quantitative receptor autoradiographic methods with radioluminography. 2. High concentrations (10(-4) - 10(-2) M) of suramin inhibited 125I-EGF binding to meningioma sections with IC50's of 3.2 +/- 0.4 x 10(-4) M, whereas lower concentrations (10(-5) - 10(-4) M) of the drug significantly enhanced EGF binding to the tumor. Scatchard analysis of EGF binding profile revealed significant increases in binding affinity following incubation in the presence of 5 x 10(-5) M suramin, without significant alterations in maximal binding capacity. 3. The addition of 10(-3) M suramin to the incubation buffer rapidly dissociated 125I-EGF previously bound to meningioma tissues as a function of time (dissociation half-life, T1/2 = 12.4 min). 4. Preincubation in the presence of 5 x 10(-5) M suramin resulted in significant increases in the subsequent binding of 125I-EGF to meningiomas, compared to findings in the control. 5. Our data indicate that (a) suramin exerts biphasic effects on EGF binding to the tissue sections of meningiomas in vitro, depending on the concentration of the drug; and (b) low concentrations of suramin enhance the affinity of the EGF receptor in the tumor sections, probably by interacting with the EGF receptor molecule rather than with the EGF peptide. 6. The functional role of increased EGF receptor affinity in meningioma sections in the presence of lower concentrations of suramin remains to be determined.
authors.affiliation: Department of Neurosurgery, Nagasaki University School of Medicine, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Tsutsumi
authors.forename: N
authors.initials: N
authors.lastname: Kitagawa
authors.forename: M
authors.initials: M
authors.lastname: Niwa
authors.forename: S
authors.initials: S
authors.lastname: Yamaga
authors.forename: H
authors.initials: H
authors.lastname: Khalid
authors.forename: K
authors.initials: K
authors.lastname: Taniyama
authors.forename: A
authors.initials: A
authors.lastname: Himeno
authors.forename: S
authors.initials: S
authors.lastname: Shibata
mesh_terms: D000368:Aged; D001345:Autoradiography; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D007700:Kinetics; D008297:Male; D008577:Meningeal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008579:Meningioma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008875:Middle Aged; D013498:Suramin / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D007457:Iodine Radioisotopes; D013498:Suramin; D004815:Epidermal Growth Factor; D066246:ErbB Receptors