To revert breast cancer cells, give them the squeeze

December 17, 2012
Shown are fluorescence images of uncompressed (left) and compressed (right) colonies of malignant breast epithelial cells. Compressed colonies are smaller and more organized. Credit: Images courtesy of Fletcher Lab

Researchers at the University of California, Berkeley, and the Lawrence Berkeley National Laboratory have put the squeeze—literally—on malignant mammary cells to guide them back into a normal growth pattern.

The findings, to be presented Monday, Dec. 17, at the annual meeting of the American Society for Cell Biology in San Francisco, show for the first time that mechanical forces alone can revert and stop the out-of-control growth of cancer cells. This change happens even though the genetic mutations responsible for malignancy remain, setting up a nature-versus-nurture battle in determining a cell's fate.

"We are showing that tissue organization is sensitive to mechanical inputs from the environment at the beginning stages of growth and development," said principal investigator Daniel Fletcher, professor of bioengineering at UC Berkeley and faculty scientist at the Berkeley Lab. "An early signal, in the form of compression, appears to get these back on the right track."

Throughout a woman's life, grows, shrinks and shifts in a highly organized way in response to changes in her reproductive cycle. For instance, when forming acini, the berry-shaped structures that secrete milk during lactation, healthy will rotate as they form an organized structure. And, importantly, the cells stop growing when they are supposed to.

One of the early hallmarks of breast cancer is the breakdown of this normal growth pattern. Not only do cancer cells continue to grow irregularly when they shouldn't, recent studies have shown that they do not rotate coherently when forming acini.

While the traditional view of focuses on the within the cell, Mina Bissell, Distinguished Scientist at the Berkeley Lab, conducted pioneering experiments that showed that a malignant cell is not doomed to become a tumor, but that its fate is dependent on its interaction with the surrounding microenvironment. Her experiments showed that manipulation of this environment, through the introduction of biochemical inhibitors, could tame mutated mammary cells into behaving normally.

The latest work from Fletcher's lab, in collaboration with Bissell's lab, takes a major step forward by introducing the concept of mechanical rather than chemical influences on cancer cell growth. Gautham Venugopalan, a member of Fletcher's lab, conducted the new experiments as part of his recently completed Ph.D. dissertation at UC Berkeley.

"People have known for centuries that physical force can influence our bodies," said Venugopalan. "When we lift weights, our muscles get bigger. The force of gravity is essential to keeping our bones strong. Here we show that physical force can play a role in the growth—and reversion—of ."

Venugopalan and collaborators grew malignant breast epithelial cells in a gelatin-like substance that had been injected into flexible silicone chambers. The flexible chambers allowed the researchers to apply a compressive force in the first stages of cell development.

Over time, the compressed malignant cells grew into more organized, healthy-looking acini that resembled normal structures, compared with malignant cells that were not compressed. The researchers used time-lapse microscopy over several days to show that early compression also induced coherent rotation in the malignant cells, a characteristic feature of normal development.

Notably, those cells stopped growing once the breast tissue structure was formed, even though the compressive force had been removed.

"Malignant cells have not completely forgotten how to be healthy; they just need the right cues to guide them back into a healthy growth pattern," said Venugopalan.

Researchers further added a drug that blocked E-cadherin, a protein that helps cells adhere to their neighbors. When they did this, the malignant returned to their disorganized, cancerous appearance, negating the effects of compression and demonstrating the importance of cell-to-cell communication in organized structure formation.

It should be noted that the researchers are not proposing the development of compression bras as a treatment for . "Compression, in and of itself, is not likely to be a therapy," said Fletcher. "But this does give us new clues to track down the molecules and structures that could eventually be targeted for therapies."

Explore further: New class of proteins allows breast cancer cells to evade tyrosine kinase inhibitors

More information: "Externally applied forces can phenotypically revert malignant breast epithelial structures," Monday, Dec. 17, 2012, 2−3:30 pm, Session: Tumor Microenvironment, presentation: 1673, poster: B1444, Exhibit Halls A-C

Related Stories

New class of proteins allows breast cancer cells to evade tyrosine kinase inhibitors

August 13, 2012
Aberrant regulation of cell growth pathways is required for normal cells to become cancerous, and in many types of cancer, cell growth is driven by a group of enzymes known as receptor tyrosine kinases (RTKs). The RTK epidermal ...

Scientists find that normal breast cells help kill cancer cells

April 13, 2011
It is well known that the human body has a highly developed immune system to detect and destroy invading pathogens and tumor cells. Now, researchers at the U.S. Department of Energy's Lawrence Berkeley National Laboratory ...

Malignant stem cells may explain why some breast cancers develop and recur

August 16, 2011
Mutations that are found in stem cells could be causing some breast cancers to develop and may be the reason the disease recurs. These abnormal cells are likely controlling cell functions in the tumor and, given they are ...

Cellular 'glue' resists breast cancer

April 20, 2012
Early detection and advances in the treatment for breast cancer have improved the chances of survival, however new avenues for treatment are still needed in the battle against this disease. New research published in BioMed ...

Recommended for you

Clear link between heavy vitamin B intake and lung cancer

August 22, 2017
New research suggests long-term, high-dose supplementation with vitamins B6 and B12—long touted by the vitamin industry for increasing energy and improving metabolism—is associated with a two- to four-fold increased lung ...

Study provides insight into link between two rare tumor syndromes

August 22, 2017
UCLA researchers have discovered that timing is everything when it comes to preventing a specific gene mutation in mice from developing rare and fast-growing cancerous tumors, which also affects young children. This mutation ...

Retaining one normal BRCA gene in breast, ovarian cancers influences patient survival

August 22, 2017
Determining which cancer patients are likely to be resistant to initial treatment is a major research effort of oncologists and laboratory scientists. Now, ascertaining who might fall into that category may become a little ...

Study identifies miR122 target sites in liver cancer and links a gene to patient survival

August 22, 2017
A new study of a molecule that regulates liver-cell metabolism and suppresses liver-cancer development shows that the molecule interacts with thousands of genes in liver cells, and that when levels of the molecule go down, ...

Zebrafish larvae could be used as 'avatars' to optimize personalized treatment of cancer

August 21, 2017
Portuguese scientists have for the first time shown that the larvae of a tiny fish could one day become the preferred model for predicting, in advance, the response of human malignant tumors to the various therapeutic drugs ...

Scientists discover vitamin C regulates stem cell function, curbs leukemia development

August 21, 2017
Not much is known about stem cell metabolism, but a new study from the Children's Medical Center Research Institute at UT Southwestern (CRI) has found that stem cells take up unusually high levels of vitamin C, which then ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.