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A window into cancer research, literally

Tiny windows implanted into mice, which allow scientists to observe their organs, may provide new insights into the spread of cancer cells.

November 03, 2012|By Monte Morin, Los Angeles Times

A tiny, porthole-shaped device that allows scientists to peer into the guts of a living mouse may provide researchers with valuable new insights into the lethal migration of rogue cancer cells.

In a procedure evocative of cows who have been fitted with cannula, or "windows," so that veterinarians can observe their digestion, scientists in the Netherlands surgically implanted glass windows in the abdomens of mice so that they could observe their livers and other organs. Researchers then used powerful microscopes to track the movements of individual cancer cells for up to a month.

The device, called an abdominal imaging window, or AIW, was described this week in the journal Science Translational Medicine. It has already shed light on a critical yet seldom-observed stage in the growth of cancer, said Jacco van Rheenen, a biophysicist at Utrecht's Hubrecht Institute and the report's senior author.

Metastasis is the process by which cancer cells leave a primary tumor and spread through the body, creating new colonies. It is also the process that kills the majority of cancer patients.

Previous studies have shown that large tumors can spawn millions of cells that are capable of entering a patient's bloodstream within 24 hours. Though very few of these cancer cells survive, those that do create new colonies that will grow — and possibly release other cells.

Although medicine has made advances in the treatment of primary tumors, slowing or halting metastasis has proved more challenging. This is due, in part, to the inability of researchers to observe cancer cells in action over extended periods. For many years, scientists have used surgical procedures to observe affected tissues, but only for a few hours at a time.

In the Dutch study, researchers located the half-inch viewing window so that it exposed the animal's liver, but still allowed the mouse to move normally. (The viewing window itself is encircled by a titanium ring that is sutured to the animal's flesh.) Scientists then placed anesthetized mice in a special viewing container and injected fluorescent colorectal tumor cells into their livers.

The researchers used a microscope and a camera to create time-lapse images of the glowing cells over a period of days. Van Rheenen and his colleagues observed that the cancer cells were highly mobile at first, wandering through the liver tissue as individual cells. By the fifth day, however, they stopped moving and had multiplied to the point that they were densely packed.

Targeting cancer cells during their short period of high mobility might help to reduce their spread, the researchers theorized, so they set out to test that idea with a drug known to reduce the movement of cancer cells.

The drug, phospholipase C inhibitor U73122, cut the average distance the cancer cells traveled in half, the authors wrote. However, it appeared to have little effect on the cancer cells once they had stopped moving. As a result, the authors said, the drug would not be a top choice for clinical study.

But the experiment's results did suggest that targeting mobile cancer cells early on — particularly after the removal of a primary tumor — might increase patient survival rates when combined with other treatments, the authors wrote.

Dr. Jochen Herms, a neuropathologist at Ludwig Maximilian University in Munich, Germany, wrote in a separate article that Van Rheenen and his colleagues had solved a long-standing problem when it comes to observing cancer cells in abdominal organs. Herms, who was not involved in the study, wrote that the window could become a valuable tool for research.

However, he was less convinced that the targeting of cell mobility might soon prove useful in humans.

"Although the authors' first results in mice are encouraging, further investigation is needed," he wrote.

monte.morin@latimes.com

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