PRODUCTION OF ACIDIC AND BASIC FIBROBLAST GROWTH-FACTOR BY THE HORMONE-INDEPENDENT BREAST-CANCER CELL-LINE MDA-MB-231

Normal, as well as the majority of malignant, mammary epithelial cells will proliferate upon stimulation by FGFs. However estrogen-independe nt MDA-MB-231 cells (which are able to grow in vitro in serum-free med ium) are not significantly stimulated by exogenous FGFs even though th ey possess high and low affinity receptors for these growth factors. B iological assays, measuring CCL39 fibroblast proliferation or PC12 phe ochromocytoma cell neurite outgrowth, demonstrated the presence of FGF activity in MDA-MB-231 cell extracts and also in the culture medium c onditioned by these cells. This biological activity decreased in the p resence of neutralizing anti-FGF antibodies. Using immunohistochemical methods FGF1 and FGF2 immunoreactivity was detected in MDA-MB-231 cel ls. After purification by heparin-Sepharose chromatography and Western blot analysis, Mr 18000 molecules showed the same physicochemical cha racteristics as FGF1 and FGF2. These results demonstrate the productio n and release of FGF related molecules by MDA-MB-231 cells and suggest an autocrine stimulation of these cells.