Faculty Bibliography

Sheep pituitary glands contain a protein that stimulates plasminogen activator (PA) activity 3- to 20-fold in serum-free cultures of T47D, MTW9/PL, and SC115 breast tumor cells. This protein was found to be similar to basic fibroblast growth factor (bFGF) in size, cationic nature, and affinity for heparin. Purified human placental bFGF, a homologue of human and bovine pituitary bFGF, was effective in stimulating mammary tumor cell PA at a concentration of 1 ng/ml. Antibodies to placental bFGF blocked the PA stimulatory activity of sheep pituitary extracts. Because of these properties, the active protein in sheep pituitary glands was identified as bFGF. This represents another function of bFGF, indicating that its spectrum of target cells is wider than previously thought. Because of previously established correlations between PA production in vitro and tumor growth in vivo, we suggest that bFGF may contribute to the growth of breast carcinomas in vivo. Other types of carcinomas may also be affected by bFGF

Several crude angiogenesis preparations, as well as a purified angiogenesis factor from human placenta, were tested for their ability to stimulate the production of plasminogen activator (PA) and collagenase activities, motility, chemotaxis, DNA synthesis and clonal growth in cultured endothelial cells. Treatment of capillary endothelial cells resulted in a stimulation of all the above activities, whereas endothelial cells derived from large vessels did not respond. These cellular activities are postulated to be responsible for capillary growth in vivo

A protein that stimulates the production of plasminogen activator and latent collagenase in cultured bovine capillary endothelial cells has been purified 10(6)-fold from term human placenta by using a combination of heparin affinity chromatography, ion-exchange chromatography, and gel chromatography. The purified molecule has a molecular weight of 18,700 as determined by NaDodSO4/PAGE under both reducing and nonreducing conditions. The purified molecule stimulates the production of plasminogen activator and latent collagenase in a dose-dependent manner between 0.1 and 10 ng of protein/ml. The purified protein also stimulates DNA synthesis and chemotaxis in capillary endothelial cells in the same concentration range. Thus, this molecule has all of the properties predicted for an angiogenic factor