Featured Research

from universities, journals, and other organizations

Cancer cells may respond to mechanical force

Date:
April 9, 2014
Source:
University of North Carolina Health Care
Summary:
The processes and cellular pathways that allow cells to move, stiffen, and react to physical stresses has been identified through new research. This knowledge, researchers hope, could reveal the causes of cancer and help develop treatments, including therapies for a variety of diseases. "In the cancer context, mechanical force is important because tumor cells will generate force as they are invading, pulling on other cells," said one researcher. "They are pulling on the cells they are attached to as they are trying to get away."

A magnetized bead attaches to the exterior of a cell nucleus. The beads allow researchers to map out the signalling pathways that activate when physical forces push and pull on a cell.
Credit: UNC/Burridge Lab

The push and pull of physical force can cause profound changes in the behavior of a cell. Two studies from researchers working at the UNC Lineberger Comprehensive Cancer Center reveal how cells respond to mechanical manipulation, a key factor in addressing the underlying causes of cancer and other diseases.

Related Articles


The studies, published in Nature Cell Biology and the Journal of Immunology, have their roots in a longtime partnership between the labs of Keith Burridge, PhD, Kenan Professor of Cell Biology and Physiology in the UNC School of Medicine, and Richard Superfine, PhD, Taylor-Williams Distinguished Professor of Physics and Astronomy in the College of Arts and Sciences.

Using equipment funded in part by the University Cancer Research Fund, researchers in Burridge's lab work to identify the processes and cellular pathways that allow cells to move, stiffen, and react to physical stresses. This knowledge, researchers hope, could reveal the causes of cancer and help develop treatments, including therapies for a variety of diseases.

"In the cancer context, mechanical force is important because tumor cells will generate force as they are invading, pulling on other cells," said Burridge, a Lineberger member. "They are pulling on the cells they are attached to as they are trying to get away."

In the Nature Cell Biologypaper, lead author Christophe Guilluy, a postdoc in the Burridge lab, showed that the nucleus of a cell responds and reacts to mechanical force. Using 2.8-4 micron metallic beads coated with a protein that binds to the exterior of the nucleus, Guilluy pulled on the beads using a series of magnetic pulses. With each pulse, the nucleus moved a fraction less than during the previous pulse, showing that the nucleus stiffened in response to the mechanical force.

Before this experiment, scientists thought that the cellular response to physical manipulation emanated from the cell surface and the cytoskeleton surrounding the nucleus and other organelles.

"We normally think of cells responding to mechanical forces at their periphery," Burridge said. "This is the first time, I think, that someone has shown that an isolated organelle can respond to mechanical force. I think it is actually a significant finding in the big picture of biology."

In the Journal of Immunology paper, lead author graduate student Elizabeth Lessey-Morillon examined the ways in which the cells lining our blood vessels stiffen and relax to allow immune system cells to pass out of the bloodstream into surrounding tissue. Cancer researchers have a particular interest in this process, as metastasizing tumor cells may use the same mechanisms to migrate through the body.

"We think metastasizing cells may essentially mimic what white blood cells do," said Burridge.

Using magnetic beads attached to the endothelial cells that line blood vessels, Lessey-Morillon discovered that applying force to the cells caused them to stiffen, opening gaps between the cells through which the white blood cells could pass. The response activated a pathway mediated by the proteins RhoA and LARG.

When she blocked the pathway, the cell stiffening response slowed. Because the pathway may also play a role in cancer metastasis, Burridge said the response could indicate that this pathway could be a viable target for future therapies.

"We think this response would be true also for tumor cells moving over the surface. They wouldn't be as competent in passing through the endothelial wall," said Burridge.


Story Source:

The above story is based on materials provided by University of North Carolina Health Care. Note: Materials may be edited for content and length.


Journal References:

  1. E. C. Lessey-Morillon, L. D. Osborne, E. Monaghan-Benson, C. Guilluy, E. T. O'Brien, R. Superfine, K. Burridge. The RhoA Guanine Nucleotide Exchange Factor, LARG, Mediates ICAM-1-Dependent Mechanotransduction in Endothelial Cells To Stimulate Transendothelial Migration. The Journal of Immunology, 2014; 192 (7): 3390 DOI: 10.4049/jimmunol.1302525
  2. Christophe Guilluy, Lukas D. Osborne, Laurianne Van Landeghem, Lisa Sharek, Richard Superfine, Rafael Garcia-Mata, Keith Burridge. Isolated nuclei adapt to force and reveal a mechanotransduction pathway in the nucleus. Nature Cell Biology, 2014; 16 (4): 376 DOI: 10.1038/ncb2927

Cite This Page:

University of North Carolina Health Care. "Cancer cells may respond to mechanical force." ScienceDaily. ScienceDaily, 9 April 2014. <www.sciencedaily.com/releases/2014/04/140409094332.htm>.
University of North Carolina Health Care. (2014, April 9). Cancer cells may respond to mechanical force. ScienceDaily. Retrieved October 30, 2014 from www.sciencedaily.com/releases/2014/04/140409094332.htm
University of North Carolina Health Care. "Cancer cells may respond to mechanical force." ScienceDaily. www.sciencedaily.com/releases/2014/04/140409094332.htm (accessed October 30, 2014).

Share This



More Health & Medicine News

Thursday, October 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Mind-Controlled Prosthetic Arm Restores Amputee Dexterity

Mind-Controlled Prosthetic Arm Restores Amputee Dexterity

Reuters - Innovations Video Online (Oct. 29, 2014) A Swedish amputee who became the first person to ever receive a brain controlled prosthetic arm is able to manipulate and handle delicate objects with an unprecedented level of dexterity. The device is connected directly to his bone, nerves and muscles, giving him the ability to control it with his thoughts. Matthew Stock reports. Video provided by Reuters
Powered by NewsLook.com
Google To Use Nanoparticles, Wearables To Detect Disease

Google To Use Nanoparticles, Wearables To Detect Disease

Newsy (Oct. 29, 2014) Google X wants to improve modern medicine with nanoparticles and a wearable device. It's all an attempt to tackle disease detection and prevention. Video provided by Newsy
Powered by NewsLook.com
Can Drinking Milk Lead To Early Death?

Can Drinking Milk Lead To Early Death?

Newsy (Oct. 29, 2014) Researchers in Sweden released a study showing heavy milk drinkers face an increased mortality risk from a variety of causes. Video provided by Newsy
Powered by NewsLook.com
Obama: The US Will Not 'run and Hide' From Ebola

Obama: The US Will Not 'run and Hide' From Ebola

AP (Oct. 29, 2014) Surrounded by health care workers in the White House East Room, President Barack Obama said the U.S. will likely see additional Ebola cases in the weeks ahead. But he said the nation can't seal itself off in the fight against the disease. (Oct. 29) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins