Inhibition of human breast epithelial HBL100 cell proliferation by a dextran derivative (CMDB7) with the FGF2 autocrine loop

Fibroblast growth factor 2 (FGF2) has been shown to be an autocrine growth factor in human breast epithelial cells HBL100. Here we studied the effects of one dextran derivative (CMDB7) on this autocrine loop. CMDB7 caused a dose-dependent decrease HBL100 growth in serum-free medium, [H-3]thymidine uptake in HBL100 cells: and Balbc/3T3 cells by exogenous FGF2 was inhibited by CMDB7. Receptor binding assays with radio-iodinated FGF2, IGF1, EGF showed that CMDB7 only displaced the binding of I-125-FGF2 in a dose dependent manner. Scatchard analysis revealed that the presence of CMDB7 reduced 78% and 82% FGF2 binding capacity to its high and low affinity receptors respectively without altering the affinites of binding sites. These results suggest that CMDB7 exert its antiproliferative action on HBL100 cells by interfering with FGF2 autocrine loop. (C) 1997 Academic Press.