Discovery of the First Stimulating Factors of Blood Vessels
The work of Judah Folkman indicated that one or more factors produced by a tumor could stimulate angiogenesis. These factors were called tumor angiogenesis factors (TAFs), and various laboratories set out to identify these TAFs. The problem was that even if the culture medium or the extracts of the tumor cells or of other tissues showed an important stimulatory activity for endothelial cells, the responsible factors could not be efficiently purified. This changed with the discovery that these factors had a strong affinity for heparin. Using heparin-sepharose chromatography, Michael Klagsbrun and Jay Shin from the Judah Folkman laboratory, and researchers from several other laboratories, were able to isolate these factors—which were called heparin-binding growth factors—and to determine their amino acid sequences [114–116] (Fig. 6.1).
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