Dr. Fridman has been awarded more than $3 million to further investigate MMPs.

When breast cancer spreads, or metastasizes, it recruits enzymes from normal cells to drill into new tissues and open pathways for the tumor cells to invade. Rafael Fridman, PhD, professor of pathology, hopes to learn how tumor cells use these enzymes, which alternatively go by the names of gelatinases, matrix metalloproteinases or MMP2s. He will conduct the research with more than $3 million from several multi-year awards: two five-year grants from the National Institutes of Health and a three-year grant from the Department of Defense.

Dr. Fridman explained that the body’s tissues constitute a barrier to tumor cell invasion in the form of an extracellular matrix, which is a scaffold composed of proteins commonly known as collagens. That barrier is compromised when metalloproteinases degrade the scaffold and clear the way for the tumor cells to enter. The damage is compounded because the metalloproteinases also induce the formation of new blood vessels in the tumor, a process called angiogenesis. With these new vessels, the tumors grow.

“One of the early findings is that the enzymes are associated with the surfaces of the tumor cells,” Dr. Fridman said. “We propose to try to identify the mechanism by which these enzymes associate with that surface and see whether there are specific receptors for the enzymes.” He and his research team hope to find the enzyme receptors, which are attachment points for the enzymes, and develop inhibitors that will prevent the enzymes from binding. “If we can do that, maybe the tumor cells will be unable to use those enzymes for metastasis.”

Already, he said, clinical trials are under way using metalloproteinase inhibitors. “After many years – and many investigators – working in this area, we now know that these enzymes play an important role and we are targeting these enzymes for anti-cancer therapies. If these therapies work out, and the inhibitors prove promising, they might be used more broadly as a cancer treatment inhibiting angiogenesis and metastasis.” He speculated, “They could be one of the next generation of anti-cancer drugs.”