Researchers isolate protein domain linked to tumor p...( Troy N.Y. When a promising cancer d...)

Troy, N.Y. When a promising cancer drug reached clinical trials in the 1990s, researchers were disappointed by the debilitating side effects that limited the trials. The drug inhibited a family of enzymes known as matrix metalloproteinases (MMPs). Now, researchers at Rensselaer Polytechnic Institute have shown that creating drugs that inactivate a different part of the MMP enzyme could have the capacity to target the tumor without the damaging side effects. Their findings, which hold promise for improved cancer therapies, were published Feb. 5 in the online Early Edition of the Proceedings of the National Academy of Sciences (PNAS).

"The failure of the clinical trials suggest that the proteinases were not only involved in the pathology of the disease, but also in maintaining the normal health of the patient," said Andrea Page-McCaw, assistant professor of biology at Rensselaer and the corresponding author of the study. Page-McCaw and her colleagues, including senior research specialist Bernadette M. Glasheen and undergraduate biology student Aasish Kabra, set out to determine the functions of different parts of an MMP enzyme. These parts, known as domains, usually correlate to a specific protein function. Inactivating one domain within a protein can often have significant and unknown consequences.

To determine MMP domain function, the researchers used a simple model organism, the common fruit fly. Unlike mouse and other mammal models that have 24 or more different and semi-redundant MMPs, the fly model has only two. This substantially simplifies the problem of understanding function of each domain, as there aren't so many other closely related proteins that can fill in if a domain on one is broken.

The researchers found that a domain known as the hemopexin domain was important for tissue invasion events. During tissue invasion, cells from one tissue invade into and usually move through another tissue, sometimes ending up in a completely differ
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