October 31, 2014
Engineers at Johns Hopkins Institute for NanoBioTechnology (INBT) have invented a lab device to give cancer researchers an unprecedented microscopic look at metastasis (spread of tumor cells, causing more than 90 percent of cancer-related deaths), with the goal of eventually stopping the spread, described in their paper in the journal Cancer Report.
“There’s still so much we don’t know about exactly how tumor cells migrate through the body, partly because, even using our best imaging technology, we haven’t been able to see precisely how these individual cells move into blood vessels,” said Andrew D. Wong, a Department of Materials Science and Engineering doctoral student and lead author of the journal article. “Our new tool gives us a clearer, close-up look at this process.”
The device replicated these processes in a small transparent chip that incorporates an artificial blood vessel and surrounding tissue material. A nutrient-rich solution flows through the artificial vessel, mimicking the properties of blood.
With this novel lab platform, Wong said, the team was able to record a video of the movement of individual cancer cells as they crawled through a three-dimensional collagen matrix. This material resembles the human tissue that surrounds tumors when cancer cells break away and try to relocate elsewhere in the body. This process is called “invasion.”
Wong also created a video of single cancer cells prying and pushing their way through the wall of an artificial vessel lined with human endothelial cells, the same kind that line human blood vessels.
By entering the bloodstream through this process, called “intravasion,” cancer cells are able to hitch a ride to other parts of the body and begin to form deadly new tumors.
The breast cancer cells, inserted individually and in clusters in the tissue near the vessel, are labeled with fluorescent tags, enabling their behavior to be seen, tracked and recorded via a microscopic viewing system.
Wong’s doctoral advisor, Peter Searson, the Joseph R. and Lynn C. Reynolds Professor of Materials Science and Engineering and director of the INBT, said Wong took on this challenging project nearly five years ago—and ultimately produced impressive results.
“In the past, it’s been virtually impossible to see the steps involved in this process with this level of clarity. We’ve taken a significant leap forward.”
This improved view should give cancer researchers a much clearer look at the complex physical and biochemical interplay that takes place when cells leave a tumor, move through the surrounding tissue and approach a blood vessel. For example, the new lab device enabled the inventors to see detailed images of a cancer cell as it found a weak spot in the vessel wall, exerted pressure on it and squeezed through far enough so that the force of the passing current swept it into the circulating fluid.
“This device allows us to look at the major steps of metastasis as well as to test different treatment strategies at a relatively fast pace,” Wong said. “If we can find a way to stop one of these steps in the metastatic cascade, we may be able to find a new strategy to slow down or even stop the spread of cancer.”
Next, the researchers plan to use the device to try out various cancer-fighting drugs within this device to get a better look at how the medications perform and how they might be improved. A provisional patent has been obtained through the Johns Hopkins Technology Transfer office.
Wong’s work has been supported by an INBT training grant. Development of the cancer research device was supported by the National Institutes of Health.