SURAMIN INHIBITS PROLIFERATION OF RAT GLIOMA-CELLS AND ALTERS N-CAM CELL-SURFACE EXPRESSION

Suramin, a drug used in the treatment of trypanosomiasis and onchocerciasis inhibits growth‐factor‐induced mitogenesis. We have investigated the effect of suramin on the growth rate and the morphology of C6 glioma cells cultured in the presence of serum or in a serum‐free defined medium. Exponentially growing cells were seeded in multi‐dish plates (5 × 104 cells/2 cm2 well) in DMEM supplemented with 5% fetal calf serum and were continuously exposed to 1 μg/ml to 1,000 μg/ml suramin. Growth rate (determined 9 days after seeding) was reduced by 5%, 33%, 56% and 97%, respectively for suramin concentrations of 1, 10, 100 and 1000 μg/ml. Similar results were obtained in serum‐free defined medium (DMEM/F12, 1:1, v:v, EGF 5 ng/ml, transferrin 5 μg/ml, selenium 10 ng/ml). Moreover, the concentration of suramin in the culture medium remained constant, demonstrating that the drug was not actively metabolized by the cells. Suramin also induced marked changes in cell morphology: the usual bipolar shape of C6 cells evolved toward a more differentiated appearance, with numerous cellular processes allowing a wide number of cell‐cell contacts. In parallel, we monitored expression of an adhesion molecule (N‐CAM) at both the mRNA and protein levels. Indirect immunofluorescence technique showed an important increase in cell surface N‐CAM expression, starting from a dose of 10 μg/ml suramin, whereas total cellular content of N‐CAM protein as well as its mRNA levels were unaffected. We also observed that the levels of expression of actin and N‐CAM mRNAs decreased by a factor of two in cells maintained in defined medium. However, the relative ratio of N‐CAM mRNA over actin mRNA was virtually unchanged following suramin treatment. Taken together, our results suggest that suramin (i) exerts a blocking effect of autocrine growth factors, (ii) interferes with the turn‐over mechanisms of N‐CAM expressed at the cell surface, either by impairing its endocytosis and/or the process of release of the N‐CAM 120 isoform. Copyright © 1990 Wiley‐Liss, Inc., A Wiley Company