Cancer cells don't take 'drunken' walks through the body

March 11, 2014

Because of results seen in flat lab dishes, biologists have believed that cancers cells move through the body in a slow, aimless fashion, resembling an intoxicated person who cannot walk three steps in a straight line. This pattern, called a random walk, may hold true for cells traveling across two-dimensional lab containers, but Johns Hopkins researchers have discovered that for cells moving through three-dimensional spaces within the body, the "drunken" model doesn't hold true.

This finding, reported in the March 4 online Early Edition of Proceedings of the National Academy of Sciences, is important because it should lead to more accurate results for scientists studying how cancer spreads through the body, often leading to a grim prognosis. To address this dimensional disagreement, the study's authors have produced a new mathematical formula that they say better reflects the behavior of cells migrating through 3D environments.

The research was supervised by Denis Wirtz, the university's Theophilus H. Smoot Professor, with appointments in the departments of Chemical and Biomolecular Engineering, Pathology and Oncology within Johns Hopkins' Whiting School of Engineering and School of Medicine. Wirtz said the discovery reinforces the current shift toward studying how cells move in three dimensions. His lab team has conducted earlier studies showing that that cells in 2D and 3D environments behave differently, which affects how cancer migrates within the body.

"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 said. "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."

The video will load shortly

For researchers trying to understand how metastasis occurs, he added, this discovery has critical implications.

"This means that the time these cancer cells need to make their way out of connective tissues is much shorter than previous estimates," said Wirtz, who was recently named the university's vice provost for research.

The co-lead authors on the PNAS paper were Pei-Hsun Wu, a postdoctoral fellow, and Anjil Giri, a doctoral student, both in the Department of Chemical and Biomolecular Engineering.

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

"It has been used for both kinds of experiments because it's easy and convenient," Wu said. "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."

The researchers discovered that cells in a 3D matrix exhibit different magnitudes of movement in different directions. To address this, the team members enhanced the original formula by identifying the primary and secondary directions in which the cells move, along with the speeds at which the cells travel and their persistence. In cell studies, persistence refers to how far the cells move in a fairly straight line before changing direction.

"Cells that are moving through a 3D environment seem to be more directional than those moving across a flat 2D surface," co-lead author Giri said. "The unpredictable 'random walk' is not prevalent in a 3D environment."

The team's improved math model for studying cell migration was published with their journal article, and the researchers hope other scientists who are trying to understand and prevent cancer metastasis will quickly adopt it. Although the team members used fibrosarcoma cancer cells in the PNAS study, they said the new model can also be used to help understand the behavior of other cell types, including those that move through the body to help fight infections and to speed the healing of wounds.

Explore further: New breast cancer stem cell findings explain how cancer spreads

More information: www.pnas.org/content/early/201 … 967111.full.pdf+html

Related Stories

New breast cancer stem cell findings explain how cancer spreads

January 14, 2014
Breast cancer stem cells exist in two different states and each state plays a role in how cancer spreads, according to an international collaboration of researchers. Their finding sheds new light on the process that makes ...

UV light aids cancer cells that creep along the outside of blood vessels

March 10, 2014
A new study by UCLA scientists and colleagues adds further proof to earlier findings by Dr. Claire Lugassy and Dr. Raymond Barnhill of UCLA's Jonsson Comprehensive Cancer Center that deadly melanoma cells can spread through ...

New 3-D stem cell culture method published

March 2, 2012
Stem cells are the body's mechanics, repairing damaged tissues and organs. Because these cells are able to grow into any type of cell in the body, scientists believe they hold the key to groundbreaking new therapies. To help ...

Recommended for you

Shooting the achilles heel of nervous system cancers

July 20, 2017
Virtually all cancer treatments used today also damage normal cells, causing the toxic side effects associated with cancer treatment. A cooperative research team led by researchers at Dartmouth's Norris Cotton Cancer Center ...

Molecular changes with age in normal breast tissue are linked to cancer-related changes

July 20, 2017
Several known factors are associated with a higher risk of breast cancer including increasing age, being overweight after menopause, alcohol intake, and family history. However, the underlying biologic mechanisms through ...

Immune-cell numbers predict response to combination immunotherapy in melanoma

July 20, 2017
Whether a melanoma patient will better respond to a single immunotherapy drug or two in combination depends on the abundance of certain white blood cells within their tumors, according to a new study conducted by UC San Francisco ...

Discovery could lead to better results for patients undergoing radiation

July 19, 2017
More than half of cancer patients undergo radiotherapy, in which high doses of radiation are aimed at diseased tissue to kill cancer cells. But due to a phenomenon known as radiation-induced bystander effect (RIBE), in which ...

Definitive genomic study reveals alterations driving most medulloblastoma brain tumors

July 19, 2017
The most comprehensive analysis yet of medulloblastoma has identified genomic changes responsible for more than 75 percent of the brain tumors, including two new suspected cancer genes that were found exclusively in the least ...

Novel CRISPR-Cas9 screening enables discovery of new targets to aid cancer immunotherapy

July 19, 2017
A novel screening method developed by a team at Dana-Farber/Boston Children's Cancer and Blood Disorders Center—using CRISPR-Cas9 genome editing technology to test the function of thousands of tumor genes in mice—has ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.