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New Hopkins device allows researchers to observe how cancer spreads

New Hopkins device allows researchers to observe how cancer spreads
This dish houses a lab chip that Johns Hopkins engineers built to gain an unprecedented closeup view of how cancer cells enter the bloodstream to spread the disease. (Will Kirk/Johns Hopkins University, Baltimore Sun)

Thin tendrils extend from the roughly circular cancer cell, breaking through the wall of an artificial blood vessel. The cell then oozes inside the blood vessel before being swept away after about a day by the artificial blood, presumably on its way to spread cancer to a body's organs.

The way cancer spreads from one organ to other parts of the body, called metastasis, has never been seen this way before. It became possible after several years of work by a Johns Hopkins doctoral candidate and his adviser on a palm-sized device that allows them to observe and replicate metastasis, which experts say is responsible for 90 percent of cancer-related deaths.

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"If you can halt or impede the metastasis process it could theoretically postpone or even stop a lot of cancer-related deaths," said Andrew Wong, the doctoral student in Johns Hopkins' department of materials science and engineering, who developed the device.

Wong and his doctoral adviser, Peter Searson, the Joseph R. and Lynn C. Reynolds Professor of Materials Science and Engineering and director of Hopkins' Institute for NanoBioTechnology, say that researchers long have understood that cancer cells break through the walls of blood vessels or lymphatic vessels to hitch a ride to other organs in the body.

But because the process was difficult to observe in a human patient or in an animal such as a mouse, they weren't sure exactly how the cancer was able to break away from the original organ it had invaded, they said.

The work involved more than just building the silicone-rubber-and-glass device, which is protected by a provisional patent obtained through the Johns Hopkins Technology Transfer Office. Wong also had to develop an artificial blood vessel, about the width of a human hair, to use inside the device to conduct the experiment. While techniques for building such artificial tissue exist, the process took years to refine, he said.

"That was a huge technological challenge," Searson said. "But there's still a long way to go to better mimic the human tissue."

To observe the metastasis process, Wong hooked up a digital camera to a microscope that peered into the device. In one case, he programmed the camera to take a picture every 10 minutes over a period of three days, then combined the images into a 40-second video that shows how the cancer cell invades the artificial vessel.

"What was very shocking and stunning about the video was that it was a very dynamic process," Wong said. The cancer cell "sends out protrusions, squid-like protrusions that stabilize in the cell wall ... it looked to us like it was able to force its way into the vessel. These little subtle aspects of it were really interesting to see."

The findings were published in the journal Cancer Research in September. Their work was supported by an Institute for NanoBioTechnology training grant and a National Institutes of Health grant.

It has been difficult to observe metastasis because a human body has many moving tissues and because the process happens rapidly, said Stuart Martin, an associate professor of physiology at the University of Maryland School of Medicine and a researcher at the University of Maryland Greenebaum Cancer Center.

Seeing how it works with Wong's device, Martin said, "allows you to do things that currently are very challenging, if not impossible, to do in a living body.

"Understanding how to develop drugs to reduce the metastasis spread is critical to increase survival," he said. "We need to take the next step and identify targets and treatments to reduce the spread, but they're well on their way. This gives them a system to ask those questions."

After having observed the first phase of the process, where the cancer breaks away from the organ it began in, Wong and Searson want to observe the second part of the process, where the cancer cells invade a new organ. They say they also plan to observe how various cancer-fighting drugs work against metastasis. Searson said scientists know cancer-fighting drugs work, but some aspects of why they do are a mystery.

"One might measure whether the animal survives or whether the tumor shrinks, and that's useful information, but it doesn't tell you what happens to the drug … how much of it is actually doing what it's supposed to do," Searson said.

Searson said he believes the device could help scientists with another medical challenge: how to get drugs into the brain. The brain's blood vessels, different from those in other parts of the body, usually act as a barrier to drugs that could treat diseases like Parkinson's or Alzheimer's. If researchers can observe how the brain's blood vessels are blocking the drugs, they may be able to develop techniques or new drugs to treat such diseases, he said.

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Wong said the project intrigued him because it seemed challenging and because he wanted to help further the study of cancer.

"It's a very prevalent disease and I thought there was not only a pressing need for better understanding metastasis, but it was a very challenging project," Wong said.

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