Engineers Design Protease Probes to Study Disease

Chemical engineers at the University of California at Santa Barbara expect that their new process to create molecular probes may eventually result in the development of new drugs to treat cancer and other illnesses. Their work, reported in the March 25, 2011 issue of Chemistry & Biology, published by Cell Press, describes a new strategy to build molecular probes to visualize, measure, and learn about the activities of enzymes, called proteases, on the surfaces of cancer cells. Dr. Patrick Daugherty, senior author and professor of chemical engineering at UCSB, explained that the probes are effective at understanding proteases involved in tumor metastasis. "Tumor metastasis is widely regarded as the cause of death for cancer patients," said Dr. Daugherty. "It's not usually the primary tumor that causes death. Metastasis is mediated by proteases, like the one we are studying here. These proteases can enable tumor cells to separate and degrade surrounding tissue, and then migrate to sites distant from the primary tumor. The tumor doesn't just fall apart. There are many events that must occur for a tumor to release cancerous cells into the blood stream that can circulate and end up in other tissues such as liver or bone." The probes allowed the researchers, for the first time, to measure directly the activity of a protease involved in metastasis. They did this by adding their probe into a dish of tumor cells. They then measured the activity of this protease that breaks down collagen –– the single most abundant protein (by mass) in the human body. "We have immediate plans to use similar probes to effectively distinguish metastatic HER2 positive tumors, one of the most commonly used biomarkers of breast cancer," said Dr. Daugherty.
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