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 gr owth factor in human breast epithelial cells HBL100. Here we studied t he effects of one dextran derivative (CMDB7) on this autocrine loop. C MDB7 caused a dose-dependent decrease HBL100 growth in serum-free medi um, [H-3]thymidine uptake in HBL100 cells: and Balbc/3T3 cells by exog enous 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 t he 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.