Cancer researchers have been using a myriad of techniques to attack tumor cells with varying success. Professor Mina Bissell of UC Berkeley and her team discovered that whether a cell becomes a cancer cell depends on the nature of its nearby environment.
Following up on that work, in collaboration with Daniel Fletcher’s Berkeley lab, they showed that a bit of mechanical pressure applied to breast cancer tumor cells led them to revert to healthy breast tissue. The findings were presented this Monday at the annual meeting of the American Society for Cell Biology in San Francisco. The researchers also point out that they don’t suggest creating a cancer fighting compression bra. “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.”
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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.
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.
UC Berkeley: To revert breast cancer cells, give them the squeeze