ABSTRACT
In an attempt to determine how cell proliferation was regulated, a number of laboratories began to isolate peptide growth factors some 25-30 years ago. Several groups, including our own, were focused on vascular growth factors, proteins that could stimulate the proliferation of endothelial cells in vitro and angiogenesis in vivo. It took us more than five years to purify a mitogen for 3T3 and endothelial cells, first from bovine cartilage, then rat chondrosarcoma, and finally human hepatoma cells. This mitogen turned out to be basic fibroblast growth factor (basic FGF), first described by Denis Gospodarowicz but not yet fully purified. The breakthrough in successful purification came about when we found that our mitogen had a very strong affinity for heparin. The introduction of heparin affinity chromatography resulted in a rapid two-step purification scheme with a high yield. It is now recognized that many growth factors are heparin binding and that these interactions are of biological significance.
