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U-M CCC - Progress Newsletter Fall 2004 Online

One of Nature's Simplest Light Sources Illuminates One of Cancer's Darkest Corners

Much progress has been made in the treatment of localized prostate cancer, and survival rates continue to rise. But for those patients facing metastatic prostate disease, no curative therapy exists. Moreover, remarkably little is known about how and why prostate cancer metastasizes, or travels, to other parts of the body. But at the U-M Comprehensive Cancer Center, numerous research initiatives are underway to learn more about prostate cancer metastasis.

In the lab of Kenneth Pienta, M.D., professor of internal medicine and urology, a remarkable product of nature is being used to track the movement of rogue cancer cells through the body. Through a process called non-invasive bioluminescent imaging (BLI), Pienta has harnessed the light of the common firefly and formulated a kind of beacon to follow cancer metastases in laboratory mice.

"The concept is useful now to help us better understand the movement of cancer through the body, and for the development of future targeted therapies for metastatic disease," explains Pienta, who is also co-director of the Urologic/Prostate Oncology Research Program at the U-M Comprehensive Cancer Center. "A firefly's glow is made up of two parts: an enzyme called luciferase, and a chemical called luciferin. In our lab, we put the gene that makes luciferase into cells from human prostate cancer tumors and inject them into lab mice.They then travel through the mouse's body as they would in a human during metastasis." Pienta's goal is to study where they go, where they stop, and how they form new tumors. The BLI process involves injecting the luciferin into the mouse. Luciferase then interacts with luciferin, causing the cells to "light up" for viewing with a special camera (see image above).

"It's a very precise process," says Linda Kalikin, Ph.D, a research

investigator working with Pienta. "We can perform analyses down to the exact number of cells present and their exact location." One example of how BLI technology is being applied is in the study of bone metastases - an area of specific interest to Pienta. Nearly every case of metastatic prostate cancer involves the spread of the disease to the bone. Using BLI, Pienta's lab has shown that cancerous cells have a tendency to gravitate toward specific places in the skeletal system - notably areas where bone is replacing itself more rapidly than normal."So sites recovering from fractures or areas where osteoporosis is setting in may be targets for metastasis," explains Pienta.

“This finding has important clinical implications.”

Another area where the firefly is “illuminating” Pienta’s work is in the evaluation of new therapies. “As treatments become more targeted and we focus on seeking out and destroying specific cells, tools like BLI will have tremendous translational value,” Pienta says. “When testing therapeutic alternatives with BLI, we can calculate how many cancer cells are killed by a given therapy at a given dose. With so much accuracy, we can evaluate ideas and move solutions from the lab to the clinic much faster.”

For more information on prostate cancer, call the U-M Comprehensive Cancer Center’s toll free Cancer AnswerLine™ at 800-865-1125 or visit our web site.

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