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.

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 July 31, 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 July 31, 2014).

Share This




More Health & Medicine News

Thursday, July 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

House Republicans Vote to Sue Obama Over Healthcare Law

House Republicans Vote to Sue Obama Over Healthcare Law

Reuters - US Online Video (July 31, 2014) The Republican-led House of Representatives votes to sue President Obama, accusing him of overstepping his executive authority in making changes to the Affordable Care Act. Mana Rabiee reports. Video provided by Reuters
Powered by NewsLook.com
Despite Health Questions, E-Cigs Are Beneficial: Study

Despite Health Questions, E-Cigs Are Beneficial: Study

Newsy (July 31, 2014) Citing 81 previous studies, new research out of London suggests the benefits of smoking e-cigarettes instead of regular ones outweighs the risks. Video provided by Newsy
Powered by NewsLook.com
Dangerous Bacteria Kills One in Florida

Dangerous Bacteria Kills One in Florida

AP (July 31, 2014) Sarasota County, Florida health officials have issued a warning against eating raw oysters and exposing open wounds to coastal and inland waters after a dangerous bacteria killed one person and made another sick. (July 31) Video provided by AP
Powered by NewsLook.com
Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
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:
from the past week

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