Epidermal Growth Factor Receptor Expression and Suramin Cytotoxicity in Vitro

Twenty-five cell lines derived from nine different human cancers were tested for the cytotoxic activity of suramin. Two different initial cellular concentrations were used: C1 (800-2000 cells per well) and C2 (3000-7000 cells per well). Suramin concentrations ranged from 50 to 2500 micrograms/ml. Cytotoxicity was assessed by the MTT test. Epidermal growth factor receptors (EGFR) were assayed by competition analysis and Scatchard plots. In sixteen cell lines suramin had an unexpected growth stimulation effect at low concentration (50-125 micrograms/ml). IC50 varied from 21 micrograms/ml (osteosarcoma, OS2) to 1408 micrograms/ml (melanoma, CAL 24) and, within melanoma cell lines, it varied from 120 micrograms/ml (CAL 41) to 1408 micrograms/ml (CAL 24). The individual IC50 values were positively and significantly linked with the initial cellular density. Eighteen cell lines had measurable EGFR (six with two families of sites, twelve with one): Kd varied between 0.004 nmol/l for the highest affinity site (melanoma, CAL 7) to 1.852 nmol/l for the lowest affinity site (lung, CAL 12). There was no relation between presence or absence of EGF binding sites and distribution of IC50, but for cells with measurable EGFR there was a weak but significant correlation between the number of EGF binding sites per cell and the corresponding IC50 (r = -0.53, P = 0.021).