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 Underwater Snail-o-Bot gets kick from light
27.02.2020 | Max-Planck-Institut für Intelligente Systeme

nachricht Existing drugs may offer a first-line treatment for coronavirus outbreak
27.02.2020 | Norwegian University of Science and Technology

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: High-pressure scientists in Bayreuth discover promising material for information technology

Researchers at the University of Bayreuth have discovered an unusual material: When cooled down to two degrees Celsius, its crystal structure and electronic properties change abruptly and significantly. In this new state, the distances between iron atoms can be tailored with the help of light beams. This opens up intriguing possibilities for application in the field of information technology. The scientists have presented their discovery in the journal "Angewandte Chemie - International Edition". The new findings are the result of close cooperation with partnering facilities in Augsburg, Dresden, Hamburg, and Moscow.

The material is an unusual form of iron oxide with the formula Fe₅O₆. The researchers produced it at a pressure of 15 gigapascals in a high-pressure laboratory...

Im Focus: From China to the South Pole: Joining forces to solve the neutrino mass puzzle

Study by Mainz physicists indicates that the next generation of neutrino experiments may well find the answer to one of the most pressing issues in neutrino physics

Among the most exciting challenges in modern physics is the identification of the neutrino mass ordering. Physicists from the Cluster of Excellence PRISMA+ at...

Im Focus: Therapies without drugs

Fraunhofer researchers are investigating the potential of microimplants to stimulate nerve cells and treat chronic conditions like asthma, diabetes, or Parkinson’s disease. Find out what makes this form of treatment so appealing and which challenges the researchers still have to master.

A study by the Robert Koch Institute has found that one in four women will suffer from weak bladders at some point in their lives. Treatments of this condition...

Im Focus: A step towards controlling spin-dependent petahertz electronics by material defects

The operational speed of semiconductors in various electronic and optoelectronic devices is limited to several gigahertz (a billion oscillations per second). This constrains the upper limit of the operational speed of computing. Now researchers from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg, Germany, and the Indian Institute of Technology in Bombay have explained how these processes can be sped up through the use of light waves and defected solid materials.

Light waves perform several hundred trillion oscillations per second. Hence, it is natural to envision employing light oscillations to drive the electronic...

Im Focus: Freiburg researcher investigate the origins of surface texture

Most natural and artificial surfaces are rough: metals and even glasses that appear smooth to the naked eye can look like jagged mountain ranges under the microscope. There is currently no uniform theory about the origin of this roughness despite it being observed on all scales, from the atomic to the tectonic. Scientists suspect that the rough surface is formed by irreversible plastic deformation that occurs in many processes of mechanical machining of components such as milling.

Prof. Dr. Lars Pastewka from the Simulation group at the Department of Microsystems Engineering at the University of Freiburg and his team have simulated such...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

70th Lindau Nobel Laureate Meeting: Around 70 Laureates set to meet with young scientists from approx. 100 countries

12.02.2020 | Event News

11th Advanced Battery Power Conference, March 24-25, 2020 in Münster/Germany

16.01.2020 | Event News

Laser Colloquium Hydrogen LKH2: fast and reliable fuel cell manufacturing

15.01.2020 | Event News

 
Latest News

New molten metal hybrid filters from TU Freiberg will make components even safer and more resistant in the future

28.02.2020 | Materials Sciences

Polymers get caught up in love-hate chemistry of oil and water

28.02.2020 | Life Sciences

Two NE tree species can be used in new sustainable building material

28.02.2020 | Architecture and Construction

VideoLinks
Science & Research
Overview of more VideoLinks >>>