"Cells that are moving through a 3D environment seem to be more directional than those moving across a flat 2D surface," says Anjil Giri. "The unpredictable 'random walk' is not prevalent in a 3D environment." (Credit: Kyle Steed/Flickr)
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Cancer cells don’t move like a ‘drunken sailor’

When cancer cells spread through the body they move quickly and efficiently, rather than, as previously thought, staggering like someone who can’t walk a straight line.

The old “drunken sailor” model of cancer metastasis arose from observations of cells moving slowly and aimlessly in flat laboratory dishes, researchers say.

But new observations in three-dimensional environments more like the body contradict the old way of thinking, says Denis Wirtz, professor of chemical and biomolecular engineering, pathology, and oncology in Johns Hopkins University’s Whiting School of Engineering and School of Medicine.

“Cancer cells that break away from a primary tumor will seek out blood vessels and lymph nodes to escape and metastasize to distant organs,” Wirtz says. “For a long time, researchers have believed that these cells make their way to these blood vessels through random walks.

“In this study, we found out that they do not. Instead, we saw that these cells will follow more direct, almost straight-line trajectories. This gives them a more efficient way to reach blood vessels—and a more effective way to spread cancer.”

For patients and for researchers trying to understand metastasis, the discovery has important implications, Wirtz says. “This means that the time these cancer cells need to make their way out of connective tissues is much shorter than previous estimates.”

The findings are published online in Proceedings of the National Academy of Sciences.

Unpredictable ‘random walk’

Researchers produced a new mathematical formula to better reflect the behavior of cells migrating through real-life 3D environments. The discovery should lead to more accurate results for scientists studying the spread of cancer.

Lead authors on the paper are Pei-Hsun Wu, a postdoctoral fellow, and Anjil Giri, a doctoral student, both in the department of chemical and biomolecular engineering.

The team knew that the Persistent Random Walk math model, developed for characterizing cell movements in flat Petri dishes, has also been used in 3D testing, yielding questionable results in the latter, Wu says.

“It has been used for both kinds of experiments because it’s easy and convenient. But it really doesn’t fit well when you are working in 3D. Our new math model works better in both 2D and 3D testing.”

“Cells that are moving through a 3D environment seem to be more directional than those moving across a flat 2D surface,” Giri says. “The unpredictable ‘random walk’ is not prevalent in a 3D environment.”

The team’s improved mathematical model was published with the journal article, and the researchers hope other scientists trying to understand cancer metastasis will quickly adopt it. Although team members used fibrosarcoma cancer cells in the study, they say the new model can also be used to help understand other cell types, including non-cancer cells that move through the body to help fight infections and to speed the healing of wounds.

The National Institutes of Health funded the work.

Source: Johns Hopkins University

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