How cells actively stop breast cancer from becoming invasive

A new study shows that the cells surrounding the breast's milk ducts form an active barrier that extends and grabs cancer cells before they spread to the rest of the body.

The American Cancer Society estimate that in 2017, there were over 310,000 new cases of breast cancer among American women.

Of these, 63,410 women had breast cancer in situ and 252,710 had invasive breast cancer.

In situ breast cancer, also called ductal carcinoma in situ, is a non-invasive form of breast cancer in which the cancer cells that line the milk ducts have not broken through the walls of the ducts and have not managed to spread to the surrounding breast tissue.

In invasive breast cancer, on the other hand, which is also called infiltrating breast cancer, cancer cells have spread beyond the ducts and can migrate through the blood and lymphatic system to other parts of the body.

To distinguish clearly between non-invasive and invasive breast cancer, physicians look at the so-called myoepithelial layer — a layer of cells surrounding those that line the interior of the milk ducts.

When cancer cells have managed to break through this layer, doctors give a diagnosis of invasive breast cancer — a form of breast cancer that is more difficult to treat.

Now, new research shows that the myoepithelial layer is not just a passive "fortress" that may or may not be invaded by cancer cells. The myoepithelium actively tries to reach out and snatch the cancer cells that are trying to escape to the rest of the body.

The new study was led by Andrew Ewald, who is a professor of cell biology at the Johns Hopkins University School of Medicine in Baltimore, MD, and the findings were published in the Journal of Cell Biology.

How the myoepithelium grabs cancer cells

Prof. Ewald explains the role of the myoepithelium, saying, "If you think about metastasis as a long race, breaking through this layer is the exit from the starting gate."

To study the role of this "starting gate," Prof. Ewald and his colleagues used a mouse model of breast cancer. They collected cells from the rodents' breast ducts and used them to produce the so-called Twist1 protein, which previous studies have associated with cancer metastasis.

As they were examining the behavior of Twist1 cells under the microscope, the scientists saw that the myoepithelium grabbed these invasive cells and pulled them back into the milk duct.

Over the course of 114 observations, this process occurred 92 percent of the time. The video below shows the myoepithelium in action:


To further confirm their findings, Prof. Ewald and team changed the myoepithelial cells' ability to contract, as well as the ratio of the myoepithelial cells to invasive cancer cells.

The scientists monitored the effects of these changes on the number of cancer cells that escaped and compared them with a normal myoepithelium.

When the researchers engineered the cells to become less contractile, the number of cancer cells that broke through the myoepithelium was three times greater than the number of cells that escaped through a normal myoepithelial "wall."

When the researchers added two myoepithelial cells to each invasive cancer cell, the number of cancer cells that escaped through the myoepithelium decreased four times more, compared with having no myoepithelium at all.

Individualized tumor behavior predictions

Prof. Ewald comments on the findings, saying, "Understanding how cancer cells are contained could eventually help us develop ways to predict a person's individualized risk of metastasis."

Study co-author Dr. Eliah Shamir also chimes in. He says the findings suggest "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," adds Dr. Shamir, who is a surgical pathology fellow at the University of California in San Francisco.

"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."

Katarina Sirka, study co-author