The researchers say the finding doubles the number of genes now known to help tumors build up a network of blood vessels to help themselves thrive. Understanding how this process occurs and how to prevent it are of major interest to cancer researchers, especially since tumors that develop without much oxygen tend to be more aggressive and deadly.
The research also may prove important in a number of other diseases that involve oxygen depletion, such as heart attacks, strokes and the blinding disorder macular degeneration, experts say. The Duke University team's findings appear in the latest issue of the Journal of the National Cancer Institute.Angiogenesis, or blood-vessel formation, is critically important to tumors, which need to keep themselves well supplied with oxygen and other nutrients to support their rapid growth. To accomplish this plumbing project, many tumors produce proteins, such as vascular endothelial growth factor (VEGF). The genes that control VEGF help cells attract piping through chemical communication with muscle fibers that can sense when tissue needs more oxygen.
As a result, many scientists and biotech companies are trying to stall tumors by attacking their ability to form new blood vessels, a process known as anti-angiogenesis. Two drugs, Endostatin and angiostatin, made a big splash several years ago when researchers reported that a combination of the two melted away tumors in rodents by cutting off their blood supply.
Yet while results of those experimental therapies in the lab and in animals have been extremely promising, experts say the approach is still far from useful for cancer patients.
In the latest study, led by Dr. Gregory J. Riggins, a Duke geneticist and pathologist, the researchers screened more than 24,500 genes turned on in a kind of brain tumor called glioblastoma multiforme, which grow with oxygen levels about 15 times lower than normal. Riggins' group identified 10 genes that appear to help budding tumors attract a network of blood vessels.
The team also found the genes were more active in tissue samples from head and neck cancer patients, as well as breast, colon and brain tumor cells in the lab. "Presumably these genes are involved in some way in protecting the cells from low oxygen conditions," Riggins says.
Several of the new vessel-promoting genes, including a close relative of a molecule called angiopoietin, appear to be as active -- or even more so -- than VEGF, he says.
The researchers are trying to isolate the precise mechanism by which these genes affect vessel formation. "What we're doing is trying to demonstrate that the protein products from these genes -- in part the angiopoietin-related gene -- [are] directly involved in signaling blood vessel growth. If we can show that, then we want to be able to inhibit its effects," he says.
"It's definitely too early to tell if targeting any of these new genes or any combination of these genes may be beneficial," but our hope is that by targeting multiple genes there may be a potential for shutting down the growth of the tumor," Riggins says.
The mirror image of such a treatment also might be useful in diseases where too little, not too much, vessel growth is the problem. These include strokes, heart attacks and certain conditions that affect the retina of the eye, Riggins says.
What To Do