Heparan sulfate proteoglycans play a dual role in regulating fibroblast growth factor-2 mitogenic activity in human breast cancer cells.

摘要: Abstract The human breast cancer cell lines MCF-7 and MDA-MB-231 differ in their responsiveness to fibroblast growth factor-2 (FGF-2). This factor stimulates proliferation well-differentiated cells, whereas the less cells are insensitive this molecule. To investigate potential regulation of FGF-2 mitogenic activity by heparan sulfate proteoglycans (HSPG), we have treated glycosaminoglycan degrading enzymes or a metabolic inhibitor proteoglycan sulfation: sodium chlorate. interaction between was assayed examining binding 125 I-FGF-2 cultures as well cationic membranes loaded with HSPG. Using showed that heparinase treatment inhibited HSPG completely abolished induced growth; chlorate decreased dose-dependent manner. demonstrates requirement adequately sulfated for growth-promoting on cells. In highly invasive which produce twice much not normally responsive exogenously added FGF-2, effect. effect dose dependent observed at concentrations 10–30 m M; higher shows level sulfation can also negatively regulate biological FGF-2. Taken together, these results demonstrate crucial role both positive negative control proliferation.