Fast, Fluid Cells Spread Cancer

New model shows how circulating cancer cells flow and accumulate, and could help with better diagnostics.

Takeishi et al., Physical Review E (2015)

Katharine Gammon, Contributor

(Inside Science) -- Just as dandelion seeds waft in the wind to spread the plant to new areas, some tumors release exploratory cells to populate new organs of the body. Now, researchers are beginning to understand more about how the cells flow and accumulate -- in the hopes of stopping them in their tracks.

The work is especially important because the vast majority of cancer-related deaths come from metastasis -- when cancer moves into another organ, different from the original cancer. At the same time, these traveling tumor cells make up only a tiny fraction of overall cells -- about one in a billion.

Researchers in Japan turned to biophysics models to understand more about the biomechanics of cell movement.

A new model aims to better understand the spread of cancer from one part of the body to another by calculating how cancer cells flow through the bloodstream depending on the width of the vessels. In this animation, a cancer cell (white ball) travels faster than most, but not all, red blood cells (flat discs) in relatively wide vessels.

Takeishi et al. Physical Review E (2015)

"We want to reveal [the] underlying mechanics in cancer metastasis," Yohsuke Imai, a bioengineer at Tohoku University in Sendai, Japan, wrote in an email. Imai explained that metastasis is a multi-step process where cancer cells first invade a blood vessel, then circulate in the bloodstream, adhere to a vessel wall, and eventually start colonizing a new organ.

In a new report, Imai and colleagues created complex models of cells moving through tiny blood vessels, to test how the tumor cells interact with blood cells in microvessels of various sizes. They wanted to understand how the cells' trajectories and velocities changed as they experience different conditions.

While blood circulation is a pure fluid mechanics process, it's never as simple as it appears, Imai explains.

"What we found is first, the flow mode changes when the gap between the wall and the cell becomes larger than the thickness of the red blood cells," he wrote. In addition, circulating cancer cells tend to move faster than the average flow of blood in small channels.

The research was published last week in the journal Physical Review E.

Eventually, it may be possible to create a device that could process tiny amounts of blood and diagnose the progress of cancer and evaluate how well anticancer drugs work. To do so would require separating the circulating cancer cells from the regular red blood cells, something that the research could help to do. One such device reported this spring, the Cluster Chip, was able to capture clusters of two or three circulating tumor cells at a time.

Imai says that the next steps in the research are to simulate how circulating tumor cells adhere to capillaries to start growing, and to develop a model of the cells' migration over time, something that might look like a weather map.

Since most cancer-related deaths are the result of tumor metastatic spread, not the growth of the primary tumor, it is extremely important to investigate how the tumor cells reach the distant sites, said Katarzyna Rejniak, a mathematical oncologist at the Moffitt Cancer Center in Tampa, Florida.

"Blood circulation is one of the routes of tumor cell transport, but laboratory experiments on circulating tumor cells are difficult since the numbers of such cells that can be found in patients' blood samples are very small," she said. That's why math-based modeling based on physical principles is an ideal way to test various properties of circulating tumor cells in the blood flow.

Rejniak added that the new work could certainly help create future microfluidic devices to study such cell transport in laboratory settings.

She pointed out that the study raises a question that needs further investigation: how squishy or deformable circulating tumor cells are.

"There is evidence that individual tumor cells are less stiff than normal cells, and thus the fluid pressures that the cells experience in circulation can also modify cells' physical properties," she said.

Understanding squishy cells and how they move will give researchers a better grasp on the metastatic process as a whole – and hopefully lead to new ways to diagnose and treat cancers.

Author Bio & Story Archive

Katharine Gammon is a freelance science writer based in Santa Monica, California, and writes for a wide range of magazines covering technology, society, and animal science.