Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists discover a dynamic cellular defense against breast cancer invasion

30.07.2018

Johns Hopkins researchers report they have demonstrated in mouse tissue grown in the lab that the cell layer surrounding breast milk ducts reaches out to grab stray cancer cells to keep them from spreading through the body. The findings reveal that this cell layer, called the myoepithelium, is not a stationary barrier to cancer invasion, as scientists previously thought, but an active defense against breast cancer metastasis.

Results of the scientists' experiments are published online July 30, 2018, in the Journal of Cell Biology.


Real-time 3D confocal time-lapse movie of Twist1-expressing epithelial cells (red) invading into the surrounding extracellular matrix and then being restrained and pulled back by normal myoepithelial cells (green).

Credit: Katarina Sirka

"Understanding how cancer cells are contained could eventually help us develop ways to predict a person's individualized risk of metastasis," says Andrew Ewald, Ph.D., professor of cell biology at the Johns Hopkins University School of Medicine and a member of the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center.

Most breast tumors begin in the cells that line the interior of breast milk ducts. These cells in turn are surrounded by myoepithelial cells, Ewald says, which work together to contract and move milk through the ducts when a baby is nursing.

This myoepithelial layer is used clinically to distinguish contained breast cancers from invasive cancers in humans. When breast cancer cells breach the myoepithelial layer, the result is so-called invasive carcinoma, which is associated with higher rates of recurrence and the need for more aggressive treatment, says Ewald.

"If you think about metastasis as a long race, breaking through this layer is the exit from the starting gate," says Ewald.

For their study, Ewald and his team engineered cells taken from the lining of mouse breast ducts to produce the protein Twist1, which works by altering gene expression and which has been linked to cancer metastasis in multiple tumor types.

To their surprise, the researchers saw that when the invasive Twist1 cells broke through the myoepithelial layer, the myoepithelial cells grabbed the cells that had gone astray and successfully pulled them back within the breast duct lining 92 percent of the time through 114 observations.

"These findings establish the novel concept of the myoepithelium as a dynamic barrier to cell escape, rather than acting as a stone wall as it was speculated before" says Katarina Sirka, a Ph.D. student from the Ewald laboratory.

To confirm that their findings were active behaviors, Ewald and his team altered two key characteristics of myoepithelial cells -- their ability to contract and their numerical ratio to the invasive cells.

First, the researchers genetically engineered mouse myoepithelial cells to deplete their smooth muscle actin, a protein that allows the cells to contract. Under that condition, the number of escaped invasive cells that broke through the myoepithelial layer increased threefold compared to control cells with a normal myoepithelium.

Likewise, the researchers found that decreasing the proportion of myoepithelial cells to invasive cells increased the number of escaped cancer cells. By adding just two myoepithelial cells for each invasive cell, the escape rate decreased fourfold compared with the spread of invasive cells with no defending barrier.

"This is important to know because it suggests that both the physical completeness of the myoepithelium and the gene expression within the myoepithelial cells are important in predicting the behavior of human breast tumors. Anywhere this layer thins or buckles is an opportunity for cancer cells to escape," says Eliah Shamir, M.D., Ph.D, who is currently a surgical pathology fellow at the University of California, San Francisco.

In the future, Ewald and his team plan to study the cellular mechanisms prompting the myoepithelial layer to react so dynamically and what makes it fail during invasive progression.

###

Support for the group's research comes from the Breast Cancer Research Foundation/Pink Agenda (BCRF-16-048, BCRF-17-048), the Metastatic Breast Cancer Network, the National Cancer Institute (U01CA217846, U54CA2101732), and the American Cancer Society (RSG-12-141-01-CSM).

COI: The authors declare no competing financial interests.

Click here to view the video that accompanies this release.

Rachel Butch | EurekAlert!

More articles from Health and Medicine:

nachricht Deep stimulation improves cognitive control by augmenting brain rhythms
04.04.2019 | Picower Institute at MIT

nachricht Black nanoparticles slow the growth of tumors
04.04.2019 | Technische Universität München

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Explosion on Jupiter-sized star 10 times more powerful than ever seen on our sun

A stellar flare 10 times more powerful than anything seen on our sun has burst from an ultracool star almost the same size as Jupiter

  • Coolest and smallest star to produce a superflare found
  • Star is a tenth of the radius of our Sun
  • Researchers led by University of Warwick could only see...

Im Focus: Quantum simulation more stable than expected

A localization phenomenon boosts the accuracy of solving quantum many-body problems with quantum computers which are otherwise challenging for conventional computers. This brings such digital quantum simulation within reach on quantum devices available today.

Quantum computers promise to solve certain computational problems exponentially faster than any classical machine. “A particularly promising application is the...

Im Focus: Largest, fastest array of microscopic 'traffic cops' for optical communications

The technology could revolutionize how information travels through data centers and artificial intelligence networks

Engineers at the University of California, Berkeley have built a new photonic switch that can control the direction of light passing through optical fibers...

Im Focus: A long-distance relationship in femtoseconds

Physicists observe how electron-hole pairs drift apart at ultrafast speed, but still remain strongly bound.

Modern electronics relies on ultrafast charge motion on ever shorter length scales. Physicists from Regensburg and Gothenburg have now succeeded in resolving a...

Im Focus: Researchers 3D print metamaterials with novel optical properties

Engineers create novel optical devices, including a moth eye-inspired omnidirectional microwave antenna

A team of engineers at Tufts University has developed a series of 3D printed metamaterials with unique microwave or optical properties that go beyond what is...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

First dust conference in the Central Asian part of the earth’s dust belt

15.04.2019 | Event News

Fraunhofer FHR at the IEEE Radar Conference 2019 in Boston, USA

09.04.2019 | Event News

 
Latest News

New automated biological-sample analysis systems to accelerate disease detection

18.04.2019 | Life Sciences

Explosion on Jupiter-sized star 10 times more powerful than ever seen on our sun

18.04.2019 | Physics and Astronomy

New eDNA technology used to quickly assess coral reefs

18.04.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>