For Medical Center researchers, the excitement generated by their recent cancer findings is two-fold. In addition to gaining a better understanding of the mechanism by which some blood vessels grow into and feed tumors, they also found that a key protein formerly believed to be located deep within the cell is also present on the surface.
Tammy Moser, the study's principal investigator and a research associate, explained that she and her research group are now going to apply what they learned by further investigating the tumor's environment.
Previous research had found that the blood clotting protein angiostatin blocks vessel formation. Thus, in the presence of angiostatin, the tumor does not receive the necessary nutrients to grow and is effectively stopped.
In their recent findings, Moser and her colleagues determined the probable mechanism by which angiostatin works; it does not allow the blood vessel cells to withstand the harsh environment surrounding the tumor.
Specifically, the blood clotting protein binds to ATPsynthase, a molecule on the cell's surface that aids in the creation of energy for the cells. This action inhibits the creation of ATP by ATPsynthase, thus depriving the cell of necessary energy.
Dr. Charles Greenberg, a professor of medicine and pathology, explained that there had been a debate within the scientific community over the mechanism by which angiostatin blocks blood vessel growth.
"This is the first evidence that angiostatin interacts with a cell surface binding protein," he said. Greenberg added that there may be a dynamic process in the tumor environment where changing extra-cellular levels of ATP could have a major impact on blood vessel growth to the cancer cells.
Moser and her colleagues are now exploring a variety of extension from this most recent research. For example, they are looking at a tumor's environment and its effects on ATPsynthase levels. The group surmises that ATPsynthase levels normally increase in the hypoxic, or oxygen-depleted area deep within a tumor. The resulting jump in ATP levels provides the cells with enough energy to survive.
"It is very likely that ATPsynthase is affected by this abnormal microenvironment," said Dr. Mark Dewhirst, a professor of radiation oncology who is collaborating on the new study.
Moser explained that creating a hypoxic environment is quite difficult, but Dewhirst already has such models available in his lab.
Moser added that the lab is also looking into the creation of fake proteins that mimic the activities of angiostatin in blocking angiogenesis. If effective, such proteins may serve as drug therapies to treat cancer.
The exact mechanism of action of angiostatin also requires further research, explained Moser and Greenberg. He added that the protein was only recently discovered to be a small part of a larger blood protein that is involved in ensuring proper levels of blood clotting. As angiostatin effectively blocks tumor growth, it may act as a defense mechanism. Moser said that researchers speculate that "it's your body's way of fighting what shouldn't be there."
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