INVOLVEMENT OF SULFATED PROTEOGLYCANS IN CONTROL OF MCF-7 BREAST-CANCER CELL-PROLIFERATION

The MCF-7 breast cancer cells exhibit remarkable growth enhancement in response to basic fibroblast growth factor (FGF-2) stimulation in a d ose dependent manner. To investigate the involvement of proteoglycans on control of FGF-2 induced proliferation, polysaccharide chains were degraded by specific enzymes. Our results showed that MCF-7 cells were unsensitive to FGF-2 after enzymatic degradation of heparin sulfate p roteoglycans (HSPG) by heparinase. After metabolic inhibition of sulph ation by sodium ch[orate, radiolabelled proteoglycans were purified an d quantified by ion exchange chromatography. Sodium chlorate treatment reduced by 70% sulfation of proteoglycans. This decrease of sulphatio n totally inhibited FGF-2-mediated proliferation. The sulphated glycos aminoglycans which were critical in FGF-2-induced proliferation were s trictly HSPG, as an addition of heparin in cell culture medium can res tore FGF-2 mitogenic activity. In contrast, other glycosaminoglycans ( chondroitin sulfate/hyaluronic acid) did not show any effect. These re sults provide clear evidence for the critical role of HSPG in FGF-2-in duced proliferation on MCF-7 breast cancer cells.