Cancer cells caught in the (metastatic) act.

Despite thorough surgical excisions and ever more sophisticated radiation and drug treatments, some cancer cells manage to get away from physicians trying to destroy them. Tumor cells that escape capture or destruction can spread to other parts of the body and start cancer anew.

Now, scientists have caught this process, called metastasis, on videotape. The images call into question theories about why refugee cancer cells settle where they do, and they offer researchers a new way to study potential treatments, says Ann F. Chambers, an experimental oncologist at the London (Ontario) Regional Cancer Center.

Most scientists study metastasis by injecting tumor cells into mice and then, weeks later, examining the tumors that form. But working with biophysicist Alan C. Groom and his colleagues at the University of Western Ontario in London, Chambers can monitor the process as it occurs.

To do this, the researchers put an anesthetized mouse on a fluorescence microscope stage positioned over the instrument's optics. They cut open the mouse and pull out the still-attached and functioning liver, lung, or muscle to be studied. Fiber-optic filaments placed at a 45 [degrees] angle to the stage light the specimen and make possible a three-dimensional view of the tissue, says Chambers.

With a video camera tuned to red wavelengths of light, the researchers record injected cancer cells as they course through the organ's blood vessels. Dye in the cells makes them fluoresce.

Typically, researchers depict cancer cells as settling in blood vessels larger than the cells themselves and sticking there because of special adhesion molecules. But the new action images reveal that the 15- to 20-micron-wide cancer cells zip by too fast to get snagged, Chambers reported this week in Orlando at the annual American Association for Cancer Research meeting. The Canadian group thinks that cancer cells may start new tumors when they get stuck in vessels too narrow for the cells to pass through.

From there, the cells make their way into nearby tissue. The Canadians have observed that after about 26 hours, all the cancer cells injected into blood vessels in chick embryo membranes have moved out of the vessels.

"We thought the [exiting] cell would just destroy everything in its path, but it seems to ooze its way through," says Chambers. "It may clear a small path [through the vessel wall]."

Surprisingly, a malignant cell can also change shape as it whizzes through the body. The cell is rotund in the liver but long and skinny as it maneuvers through vessels that supply blood to muscle, Chambers says.

Scientists had thought that cancer cells burst if the pressure inside blood vessels becomes too great; instead, the cells pinch off bits of their cytoplasm and remain functional, she adds.

The team hopes to quantify metastasis and expects video microscopy to enable pharmaceutical companies to watch how new drugs affect this process.