By: Jean Johnson for Medtech1
Researchers at the University of Wisconsin-Madison are careful to say that it’s premature to make sweeping statements about their discovery, but their excitement is palpable.
“We have discovered a new peptide that clearly suppresses angiogenesis via a novel multi-component mechanism,” Emery Bresnick, PhD, the senior author of the study that appeared in a September 2006 issue of the Journal of Cell Biology, said in a UW-M news release. Bresnick is a professor of pharmacology and member of the UW-M Paul P. Carbone Comprehensive Cancer Center.
|Lung and bronchial cancer had the highest mortality rate for both men and women in 2006.|
More women were diagnosed with breast cancer than any other cancer in 2006, and more men were diagnosed with prostate cancer.
For more cancer statistics, see the American Cancer Society's Annual Report at http://www.cancer.org/ downloads/STT/CAFF2006 PWSecured.pdf
The National Cancer Institute is also a good resource: www.cancer.gov
For an un-dated list of ongoing and currently planned clinical trials involving angiogenesis inhibitors, including phone numbers for obtaining additional information, refer to the National Cancer Institute Cancer Trial website at http://www.cancer.gov/ clinicaltrials/developments/ anti-angio-table
He added: “A key question is whether we can exploit it to develop therapeutics. It’s premature to call it a master switch, but intriguingly, it regulates at least four different processes, each of which individually would be anti-angiogenic.”
Bresnick also cited “outstanding collaborators at the University of Wisconsin-Madison who facilitated this multidisciplinary study and co-authored this paper.” These collaborators were Patricia Keely, PhD in the department of pharmacology; a pair of researchers in the department of anatomy, John Fallon, PhD, and Tim Gomez, PhD; Sam Gellman in the department of chemistry; and post-doctoral fellow Souman Paul, PhD.
There’s no way around it: Bresnick and his colleagues’ unexpected findings require some understanding of just how it is that cancer mestastasizes, or begins in one area of the body and spreads to other areas. We promise to keep it simple, so read on if you’re curious about cutting-edge research as it applies to cancer.
Cancer cells have the ability to penetrate the lymphatic system and blood vessels. From there, they circulate through the bloodstream and invade normal tissues elsewhere. As the National Cancer Institute (NCI) notes, “metastasis requires angiogenesis,” which simply means that once the cells establish themselves at a new point, they need a new network of blood vessels in order to grow. It is this process of forming new blood vessels that is called angiogenesis.
Angiogenesis can be quite welcome and occurs any time the body needs to create a new network of blood vessels. Angiogenesis during pregnancy, the menstrual cycle, and as a part of wound healing, for example, are normal processes.
Angiogenesis and Cancer
Tumor angiogenesis, however, “is the proliferation of a network of blood vessels that penetrates into cancerous growths, supplying nutrients and oxygen and removing waste products,” states the NCI.
The relationship between angiogenesis and cancer is not new, but has developed out of research beginning in the 1960s. Prior to that time experts thought tumors got the blood they needed via enlargement or dilation of the associated blood vessels.
In animal experiments with rats, however, scientists found that a new network of blood vessels – developed through angiogenesis – was vital to the growth of tumors. “Without angiogenesis,” the NCI explains, “tumor growth stopped.”
Once results were checked and double checked – and researchers confirmed the opposite as well: that with angiogenesis, tumors grew. Thus, the quest began to find out what prompted the body to grow these dense networks of new blood vessels proximate to cancer cells.
Scientists found that the cancer cells themselves contained “activator molecules” that then contained two particular proteins that seemed to be the most important in sustaining tumor growth. One of the proteins – a substance dubbed the vascular endothelial growth factor or VEGF – is worth mentioning since Bresnick’s new research deals with it.
VEGF activates endothelial cells. In turn these cells migrate into the surrounding tissues and begin to divide. As the NCI puts it, “Soon they organize into hollow tubes that evolve gradually into a mature network of blood vessels.”
To sum up: a cancer cell plants itself somewhere in the body. It then sends out a VEGF signal to certain other cells. These cells then turn into a new series of blood vessels (angiogenesis) whose sole purpose is to feed the cancerous tumor.
The Quest for Angiogenesis Inhibitors
Once this process was understood, researchers began looking for substances that might ‘turn off’ or inhibit the formation of this critical network of blood vessels. As various experiments had already suggested, if the cancer had no source of nourishment, it could not grow.
Scientists around the globe began to identify various angiogenesis inhibitors in animal experiments and eventually human clinical trials as they increasingly identified promising areas of research. By June 2006 the U.S. Food and Drug Administration (FDA) had approved a compound that inhibits VEGF for treating colon cancer, the second-leading cause of cancer death in the United States.
Even though many questions have been answered, many remain. In particular, experts are still not clear on what side effects might be triggered when interfering with bodily processes at this level. Consequently, they are proceeding cautiously.
Bresnick Research – NK-B Receptors on Cells That Feed Cancer
With this rudimentary science in place, it is easier to understand Bresnick’s discovery. When Bresnick and his team started their study, they were not looking into angiogenesis at all. Rather according to the news release, “they were studying a protein that regulates the maturation of red blood cells and noticed that it turns on a gene that makes a compound called neurokinin-B (NK-B).”
As Bresnick puts it, the team was puzzled. “Why would a protein involved in blood-cell formation turn on the gene for a compound that is supposedly involved in regulating the nervous system?”
What they found was large numbers of NK-B receptors on endothelial cells which line the blood vessels. More, they discovered that when they added NK-B to the endothelial cells, “they lost the capacity to organize in three dimensions to form the tubes that are the precursors to new blood vessels,” explained Bresnick.
“Then we got excited,” he adds.
And so did the Wisconsin Alumni Research Foundation that has applied for a patent on the discovery. Whether or not researchers at UW-M are really onto something remains to be seen. Nevertheless, the findings are impressive enough to have heads turning.
Perhaps it is a “master switch” of sorts for cancer – then again, perhaps not. Either way, scholars are probing the body’s physiology with greater sophistication – and hoping, in the process, to give modern society tools for addressing at least one type of disease that strikes human beings so very pervasively.