Probe May Detect Early Cancer

Their findings were reported in the August 14, 2005, issue of Nature Chemical Biology.

A molecule that can label proteases--protein-chewing enzymes that blast into overdrive in cancerous cells--has been created by Matthew Bogyo, Ph.D., assistant professor of pathology, and colleagues at Stanford University School of Medicine (Palo Alto, CA, USA). The new molecule contains a fluorescent tag that flashes brightly enough to be seen with conventional imaging equipment.

This new activity-based probe is unusual in that it only lights up when the proteases are active. Since it works in living cells, the probe could potentially be used for whole-body imaging for the detection of early warning signs of cancer. Proteases work overtime in tumors that are getting ready to spread, or metastasize, and in angiogenesis. Other cells with hyperactive proteases include cells affected by arthritis, osteoporosis, atherosclerosis, and neurodegenerative disorders such as Alzheimer's.

"This is an important tool for understanding the biochemistry of proteases, and how they play a role in diseases like cancer,” said Dr. Bogyo. "And it's noninvasive and fairly nontoxic, in that it doesn't involve radioisotopes.”

The probe has a number of advantages over other enzyme imaging probes. In one innovation, the scientists added a chemical subunit called a quencher that keeps the probe dark until the protease is activated. The chemical changes activating the enzyme switch the probe on "like a molecular beacon,” noted Dr. Boygo. Since the probe is small enough to pass easily across cell membranes, it can be used inside living cells. The probe also forms a permanent bond with its targeted protease, allowing it to track where the protease is active.

In addition to making new probes, Dr. Bogyo and his team are working on imaging applications. "We have made the tool, now we want to go and use it,” observed Galia Blum, a postdoctoral scholar in Dr. Bogyo's lab and the study's lead author. "Our next step is to generate whole-body images in mice.”





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