UC Berkeley and the Lawrence Berkeley National Laboratory have literally put the squeeze on malignant breast cancer cells to guide them back into a normal growth pattern.
The findings, presented last month at the annual meeting of the American Society for Cell Biology, showed for the first time that mechanical forces alone can revert and stop the out-of-control growth of cancer cells.
And, it seems, 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 Berkeley. “Compression, appears to get these malignant cells back on the right track.”
Throughout a woman’s life, breast tissue grows, shrinks and shifts in a highly organized way in response to changes in her reproductive cycle. For instance, when forming the berry-shaped structures that secrete milk during lactation, healthy breast cells rotate as they form an organized structure.
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.
While the traditional view of cancer focuses on genetic mutations within the cell, scientists at the Berkeley Lab showed that a malignant cell is not doomed to become a tumor. Instead, its fate is dependent on its interaction with the surrounding microenvironment. Better still, manipulation of this environment can tame mutated mammary cells into behaving normally.
“People have known for centuries that physical force can influence our bodies,” said researcher Gautham 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 cancer cells.”
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 during the first stages of cell development. Over time, the compressed malignant cells grew into more organized, healthy-looking structures, compared with malignant cells that were not compressed. 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.
While researchers are not proposing compression bras as a treatment for breast cancer, they say their work provides new clues to track down the molecules and structures that could eventually be targeted for therapies.
All of which is good news for the girls!