Compressing Cancer Cells Can Stop Out-of-Control Growth
California researchers show that genes are not the only way to restore normal growth to breast cancer cells.
-- by Suzanne Boothby
For the first time ever, scientists can now show that mechanical forces alone can revert and stop cancer cell growth, even when genetic mutations are still present in a cell. University of California, Berkeley, and the Lawrence Berkeley National Laboratory researchers are literally squeezing malignant mammary cells to guide them back to normal growth patterns.
The new research presented this week at the annual meeting of the American Society for Cell Biology in San Francisco introduces the groundbreaking concept of mechanical rather than chemical influences on cancer cell growth.
"People have known for centuries that physical force can influence our bodies," says study author Gautham Venugopalan, who recently completed his Ph.D. dissertation at UC Berkeley. "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."
Throughout a woman's life, breast tissue grows, shrinks, and shifts in a highly organized way in response to changes in her reproductive cycle. One of the early hallmarks of breast cancer is the breakdown of this normal growth pattern and cells continuing to grow irregularly when they shouldn't.
About 1 in 8 women in the United States will develop invasive breast cancer during her lifetime.
The Expert Take
This structural approach to cancer cell formation is a novel approach that could lead to many new treatment options.
"We are showing that tissue organization is sensitive to mechanical inputs from the environment at the beginning stages of growth and development," says 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."
While the traditional view of cancer development focuses on the genetic mutations within the cell, Mina Bissell, Distinguished Scientist at the Berkeley Lab, was the first to claim that a cell's microenvironment plays a role in the formation of tumors. She has proved that cancer is not only caused by cancer cells, but by an interaction between cancer cells and the surrounding cellular microenvironment.
“Microenvironment and the context around those cells are actually telling the cancer gene and the cancer cell what to do,” Bissell said in a 2012 TED Talk. “Context overrides. In different contexts, cells do different things.”
Source and Method
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 cells that resembled normal structures, compared with malignant cells that were not compressed.
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. The cells stopped growing once the breast tissue structure was formed, even though the compressive force had been removed.
While the new finding is an exciting first step toward new cancer therapies, the researchers are not proposing the development of compression bras as a treatment for breast cancer.
"Compression, in and of itself, is not likely to be a therapy," says Fletcher. "But this does give us new clues to track down the molecules and structures that could eventually be targeted for therapies."
Bissell’s landmark 1997 study found that mutated mammary cells, when dosed with an antibody and placed into a normal cellular microenvironment, behaved normally.
A 2012 study describes how mouse primary epithelial cells and cell lines are cultured in relevant 3D microenvironments. The mammary gland is an ideal "model organism" for studying tissue specificity and gene expression in mammals, because it is one of the few organs that develops after birth and undergoes multiple cycles of growth, differentiation, and regression during the animal's lifetime in preparation for the important function of lactation.