Tumor cells prefer easy way out, study shows

Tumor cells become lethal when they spread. Researchers have thought they might migrate by brute force, actively pushing through tissue in their way, but it turns out tumor cells may be more methodical. Cornell biomedical engineers report in a new study that tumor cells take advantage of already-cleared paths to migrate unimpeded.

“We are looking for novel ways of preventing cancer cells of the primary tumor from spreading to other parts of the body,” said Cynthia Reinhart-King, associate professor of biomedical engineering and senior author on the study published earlier this month in the American Journal of Physiology – Cell Physiology. “Our study points to potential therapeutic targets that could be inhibited to halt tumor cell movement.”

The body’s tissue is full of small gaps between proteins and cells. Much of the research into tumor cell migration, however, has represented tissue as a solid gel. While this model has been useful in understanding how tumor cells invade, scientists are not sure if moving through an environment like the body with nonuniform consistency involves the same machinery. Some studies have supported that pre-existing spaces and tracks join together into tunnels that tumor cells can use to migrate and spread.

Reinhart-King and colleagues examined how tumor cells move, using a more accurate model of the tissue environment consisting of a microfabricated device with cell-sized tracks.

“Numerous groups, including our own, have studied how cells move. We now know, however, that how cells move depends on the structure of the environment in which they are moving. Ours is the first study to rebuild the native tracks and gaps that exist in tissue to investigate how cells use these as superhighways to move quickly to spread throughout the body,” Reinhart-King said.

The researchers found that when working through an environment with no pre-existing tracks, tumor cells had to actively stick to the tissue, break it down and then move themselves forward. In contrast, moving through tissue with paths was much easier because once the cells found the tunnels, they could avoid their tissue-clearing processes and pass through unhampered.

The findings support the idea that tumor cells prefer preformed tunnels for migration. The study also suggests that targeting the machinery that makes cells mobile, rather than targeting the tissue-clearing process – which has been tested in patients with little success – may be a better treatment strategy to stop cancers from spreading.

The article, “Comparative mechanisms of cancer cell migration through 3D matrix and physiological microtracks,” was highlighted as an April “best of the best” as part of the American Physiological Society’s select program. The work was supported by the Cornell Center on the Microenvironment and Metastasis through the National Cancer Institute, as well as the National Science Foundation.

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Melissa Osgood