DALLASThe antitumor powers of a venom protein from the
southern copperhead snake are being studied at the University of
Southern California. Results of early studies suggest that the
protein, contortrostatin (CN), combines antagonism of breast cancer
progression and inhibition of angiogenesis, making it a unique agent
for control of breast cancer growth and proliferation.
The studies used a metastatic breast cancer model, which involves
implanting human breast cancer cells into the mammary fat pads of
nude mice, principal investigator Francis S. Markland, Jr., PhD, said
at the Susan G. Komen Foundation National Grant Conference.
The researchers found that palpable tumor masses developed in the
mouse mammary tissue 2 weeks after cancer cell implantation, and that
tumor cells spread to the lungs in untreated animals within 12 weeks.
CN or placebo was injected daily into tumors in several different
groups of mice. Following treatment, the tumor masses in the
CN-treated mice were significantly smaller than those in the
Even more exciting, the CN-treated group showed more than 70%
inhibition of metastasis to the lungs, compared with the placebo
group, Dr. Markland said.
Other findings so far:
CN blocked the attachment of breast cancer cells to proteins, which
are essential components of blood vessel walls.
CN prevented cancer cell invasion through an artificial blood vessel wall.
CN inhibited new blood vessel formation induced by breast cancer
cells after incubation on a chick embryo membranous respiratory organ
(the chorioallantoic membrane), while placebo treatment did not (see Figure).
Pharmacology studies suggest that CN blocks the function of several
subclasses of cell surface proteins known as integrins, which
regulate the interaction of the cancer and vascular endothelial cells
and their microenvironment.
The genetic code for CN has been isolated and deciphered, and a
method of producing large quantities of the protein has been
established using genetic engineering technology, Dr. Markland said.
The clinical potential of this research will be advanced by the
development of targeted delivery systems that enable IV
administration of the drug, he said.