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.
According to researchers from the University of California at Berkeley and the Lawrence Berkeley National Laboratory, placing mechanical force on malignant mammary cells can actually reverse their irregular growth process and put them back on track for a normal growth pattern.
"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 malignant cells back on the right track," he stated.
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 acini, the berry-shaped structures that secrete milk during lactation, healthy breast cells 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.
Through a previous experiment at the Berkeley Lab, researchers showed it was possible to prevent these malignant cells from transforming into a tumor by manipulating the cells’ surrounding environment through the use of biochemical inhibitors. Ultimately the surrounding healthy cells could persuade the cancerous cells to grow normally again.
The most recent work from the Berkeley Lab utilizes the same concept, but introduces mechanical inhibitors rather than chemical inhibitors. The researchers grew malignant breast epithelial cells in a gelatin-like substance, which was injected into flexible silicon chambers. They then applied force to the silicon over time, and ultimately witnessed the malignant cells grow into more healthy-looking cells. Time-lapse microscopy showed the change in the compressed breast cells over time.
While the traditional view of cancer development focuses on the genetic mutations 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.
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.
Researchers further added a drug that blocked E-cadherin, a protein that helps cells adhere to their neighbors. When they did this, the malignant cells returned to their disorganized, cancerous appearance, negating the effects of compression and demonstrating the importance of cell-to-cell communication in organized structure formation.
The findings were to be presented at the annual meeting of the American Society for Cell Biology in San Francisco.
Karen Foster is a holistic nutritionist, avid blogger, with five kids and an active lifestyle that keeps her in pursuit of the healthiest path towards a life of balance.