Team discovered that cells use bradykinin to metastasize, and an approved angioedema drug could block this process.
Researchers at the University of Alabama at Birmingham (UAB) are reporting that they may have found a way to stop glioma from spreading by using a drug already approved in Europe. They discovered that bradykinin, a peptide that increases the size of blood vessels, is the mechanism glioma cells use to find blood vessels.
Glioma cells carry a receptor for bradykinin, called the B2R receptor. The researchers introduced a B2R inhibitor known as HOE 140, a laboratory version of Icatibant, a medication sanctioned in Europe for hereditary angioedema.
HOE 140 bound to the B2R receptor on glioma cells, interfering with the receptor’s opportunity to bind to bradykinin. “We found that 77 percent of glioma cells with bradykinin were able to locate a blood vessel and tap into its nutrients,” explains Vedrana Montana, Ph.D., co-author of the research, which is published March 30 in the Journal of Neuroscience. “However, when we blocked the B2R receptors from interacting with bradykinin, only 19 percent of glioma cells were able to find a blood vessel.”
“Targeting the B2R receptors is an elegant and so far unexplored approach to treat gliomas, one of the most devastating types of brain tumor,” says Harald Sontheimer, Ph.D., director of the UAB Center for Glial Biology in Medicine and senior author on the paper. “Icatibant, which is already in use in Europe, and its ability to block B2R receptors may prove to be a very promising target for further investigation.”
The researchers used human glioma cells transplanted into a mouse model. With time-lapse techniques on a laser-scanning microscope, they tracked the ability of the cells to navigate to blood vessels by means of fluorescent markers attached to the cells.