Scientists at UC San Francisco and California Biotechnology Inc. have isolated and cloned the gene for a protein that stimulates the growth of blood vessels and capillaries. The new protein could be valuable for promoting the healing of skin injuries and other wounds if it can be produced in large quantities.
Perhaps even more important, isolation of the protein also should make it easier to develop a drug that could block blood vessel growth. Such a drug would be useful in treating tumors and other diseases, such as the eye disease diabetic retinopathy, that are characterized by the proliferation of blood vessels.
The cloning of the new material, called fibroblast growth factor or FGF, was announced Friday at a meeting of the American Society for Microbiology in Washington by John Fiddes of Mountain View-based Cal Bio.
Similar to Angiogenin
FGF is similar in its effects to another protein, called angiogenin, whose isolation and cloning was announced in September by Burt Vallee, a Harvard University researcher. The structure of FGF is different from that of angiogenin, however, as is its mechanism of action.
Fiddes and his colleagues have shown that "FGF directly stimulates the proliferation of epithelial cells," which are the primary structural component of blood vessels, according to Judy Abraham of Cal Bio. "Angiogenin does not stimulate that proliferation, and its mechanism of action is not known," she said in a telephone interview.
Substances that stimulate the recruitment and growth of new blood vessels--a process called angiogenesis--were first isolated in the early 1970s by researchers at Children's Medical Center in Boston. These so-called angiogenesis factors are particularly common in tumors, which must recruit new blood vessels in order to obtain nutrients for further growth.
Angiogenin was, in fact, isolated by Vallee from a tumor.
The substances have subsequently been found in healthy organs, including the eye, the pituitary gland and corpus luteum, a tissue in the ovary. Dennis Gosporodowicz of UCSF isolated and purified FGF from the pituitary gland of cows.
Several other scientists have isolated angiogenesis factors, but in most cases the quantities were too small to permit determination of their structures.
Agents Viewed as Useful
Apparently no one has shown yet that angiogenesis factors can promote wound healing, but the growth of new blood vessels is known to be an important factor in such healing so it is generally believed that agents like angiogenin and FGF will be useful.
Scientists have also isolated several naturally occurring agents that block angiogenesis but they have not obtained enough of the materials to determine their structures.
Some scientists suspect that defects in the metabolism of the angiogenesis factors and inhibitors may be responsible for such diseases as diabetic retinopathy, in which capillaries grow into the eye and block vision.
Folkman has found that protamine, a large protein isolated from sperm, is a potent blocker of angiogenesis. Studies in mice have shown that protamine can cause as much as a 97% inhibition of lung tumor growth in mice. But protamine has too many side effects to be used in humans.
Folkman's demonstration of its activity against tumors, however, suggests that other drugs that block angiogenesis could be very powerful anti-tumor agents.