Featured Research

from universities, journals, and other organizations

'Velcro protein' found to play surprising role in cell migration

Date:
March 13, 2014
Source:
Johns Hopkins Medicine
Summary:
Studying epithelial cells, the cell type that most commonly turns cancerous, researchers have identified a protein that causes cells to release from their neighbors and migrate away from healthy mammary, or breast, tissue in mice. "Our goal is to improve outcomes for patients with metastatic breast cancer, and this work takes us one step closer to doing so," says the lead author.

Normal epithelial cells (red) in this fragment of a mouse mammary duct form branched structures. However, cells that turn on the gene Twist1 (green) detach from neighboring cells and migrate into the surrounding environment.
Credit: Eliah Shamir

Studying epithelial cells, the cell type that most commonly turns cancerous, Johns Hopkins researchers have identified a protein that causes cells to release from their neighbors and migrate away from healthy mammary, or breast, tissue in mice. They also found that deletion of a cellular "Velcro protein" does not cause the single-celled migration expected. Their results, they say, help clarify the molecular changes required for cancer cells to metastasize.

Because epithelial cells give rise to 85 percent of all cancers, the work may have implications outside of breast cancer. A summary of the results was published online on March 3 in The Journal of Cell Biology.

Epithelial cells line the inside and outside of organs throughout the body. The team focused their work on mammary epithelial cells, which form the ducts that carry milk within the breast. "Tumor cells have to break their connections to other epithelial cells in order to leave the breast and build metastases in other parts of the body," explains Andrew Ewald, Ph.D., assistant professor of cell biology and oncology at the Johns Hopkins University School of Medicine.

For their study, Ewald's team removed small pieces of mammary tissue from normal mice and grew them in gels that mimic their natural environment. By using colored proteins to mark different types of cells, they were able to use microscopes to watch how cell behavior varied with the genetics of the cells.

The first protein they studied was E-cadherin, which is found on the surface of most epithelial cells and is used to connect epithelial cells to each other. E-cadherin is like the Velcro that holds epithelial cells together, and its absence is often associated with human breast cancers, says Ewald.

In one experiment, the team deleted the protein from normal mouse mammary cells and watched what happened. Expecting the cells to completely disconnect and move out on their own into the surrounding gel, the researchers were surprised to find that most of the epithelial cells remained connected to each other, although their organization was disrupted. Some of the epithelial cells did penetrate the gel, but usually in single-file "columns" that remained connected to the tissue. A similar result was seen in live mice.

"For tumor cells to metastasize, they have to begin interacting with the proteins outside of the tumor and eventually strike out on their own," says Eliah Shamir, a graduate student in Ewald's lab and lead author on the study. "When we deleted E-cadherin, the epithelial cells began interacting more with proteins in the gel, but they didn't lose contact with the rest of the mammary tissue."

In a second set of experiments, the team turned on a gene called Twist1, which is thought to affect the activity of many genes needed to transform groups of stationary epithelial cells into independent, mobile cells. The result, they say, was dramatic. Within 24 hours of turning on Twist1, dozens of individual cells began to move past the epithelial boundary and into the gel beyond. Again, similar results were seen when the experiment was repeated in live mice.

Surprisingly, the researchers say that when they caused epithelial cells lacking E-cadherin to turn on Twist1, the cells were no longer able to escape into the gel as single cells. Instead, they created many "columns" of cells, which didn't detach from the mammary tissue. These results suggest that the single-celled detachment and migration induced by Twist1 actually requires the presence of E-cadherin -- the Velcro protein that helps bind the cells together. "This finding is quite counterintuitive," Ewald says, "and we are eager to understand the biology behind it."

Since Twist1 is known to affect the activity of many genes, the researchers have begun to narrow down which of those genes is responsible for the cellular spread they witnessed. With that information, they hope to identify new means of preventing metastasis.

"Our goal is to improve outcomes for patients with metastatic breast cancer, and this work takes us one step closer to doing so," says Ewald.


Story Source:

The above story is based on materials provided by Johns Hopkins Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. E. R. Shamir, E. Pappalardo, D. M. Jorgens, K. Coutinho, W.-T. Tsai, K. Aziz, M. Auer, P. T. Tran, J. S. Bader, A. J. Ewald. Twist1-induced dissemination preserves epithelial identity and requires E-cadherin. The Journal of Cell Biology, 2014; 204 (5): 839 DOI: 10.1083/jcb.201306088

Cite This Page:

Johns Hopkins Medicine. "'Velcro protein' found to play surprising role in cell migration." ScienceDaily. ScienceDaily, 13 March 2014. <www.sciencedaily.com/releases/2014/03/140313122538.htm>.
Johns Hopkins Medicine. (2014, March 13). 'Velcro protein' found to play surprising role in cell migration. ScienceDaily. Retrieved July 29, 2014 from www.sciencedaily.com/releases/2014/03/140313122538.htm
Johns Hopkins Medicine. "'Velcro protein' found to play surprising role in cell migration." ScienceDaily. www.sciencedaily.com/releases/2014/03/140313122538.htm (accessed July 29, 2014).

Share This




More Plants & Animals News

Tuesday, July 29, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Deadly Ebola Virus Threatens West Africa

Deadly Ebola Virus Threatens West Africa

AP (July 28, 2014) West African nations and international health organizations are working to contain the largest Ebola outbreak in history. It's one of the deadliest diseases known to man, but the CDC says it's unlikely to spread in the U.S. (July 28) Video provided by AP
Powered by NewsLook.com
Traditional African Dishes Teach Healthy Eating

Traditional African Dishes Teach Healthy Eating

AP (July 28, 2014) Classes are being offered nationwide to encourage African Americans to learn about cooking fresh foods based on traditional African cuisine. The program is trying to combat obesity, heart disease and other ailments often linked to diet. (July 28) Video provided by AP
Powered by NewsLook.com
Asteroid's Timing Was 'Colossal Bad Luck' For The Dinosaurs

Asteroid's Timing Was 'Colossal Bad Luck' For The Dinosaurs

Newsy (July 28, 2014) The asteroid that killed the dinosaurs struck at the worst time for them. A new study says that if it hit earlier or later, they might've survived. Video provided by Newsy
Powered by NewsLook.com
Raw: Sea Turtle Hatchlings Emerge from Nest

Raw: Sea Turtle Hatchlings Emerge from Nest

AP (July 27, 2014) A live-streaming webcam catches loggerhead sea turtle hatchlings emerging from a nest in the Florida Keys. (July 27) 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:
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