Study Shows How Breast Cancer Cells Break Free To Spread In The Body

 Pictured are MCF-7 human breast cancer cells, stably transformed with SNAIL (right) or an empty vector control (left). Cells expressing SNAIL show an increased mesenchymal phenotype and malignant characteristics. The control cells display a cobblestone morphology, whereas cells overexpressing SNAIL are more elongated.
 Pictured are MCF-7 human breast cancer cells, stably
transformed with SNAIL (right) or an empty vector control (left).
Cells expressing SNAIL show an increased mesenchymal
phenotype and malignant characteristics. The control cells
display a cobblestone morphology, whereas cells
overexpressing SNAIL are more elongated.
(Credit: McGrail, et al., FASEB 2014.)
More than 90 percent of cancer-related deaths are caused by the spread of cancer cells from their primary tumor site to other areas of the body. A new study has identified how one important gene helps cancer cells break free from the primary tumor.
 
A gene normally involved in the regulation of embryonic development can trigger the transition of cells into more mobile types that can spread without regard for the normal biological controls that restrict metastasis, the new study shows. Analysis of downstream signaling pathways of this gene, called SNAIL, could be used to identify potential targets for scientists who are looking for ways to block or slow metastasis. The study was published in the Journal of the Federation of American Societies for Experimental Biology (FASEB).
 
The researchers show how overexpression of the gene SNAIL in vitro allows breast cancer cells to operate independently of the mechanics of the environment inside the body. Growing evidence suggests that cancer cells metastasize by hijacking the process by which cells change their type from epithelial (cells that lack mobility) to mesenchymal (cells that can easily move). In the new study, the researchers examined the biophysical properties of breast cancer cells that had undergone this epithelial to mesenchymal transition (through overexpression of SNAIL).
 
The research team measured the mechanical properties within the nucleus and cytosol of breast cancer cells, and then measured the surface traction forces and the motility of the cells on different substrates. They found that cells became much softer, which could help them spread throughout the body.
 
The researchers used microarray analysis to examine changes in genes related to the observed biophysical changes. They found that regardless of the substrate that the cells were grown on, cells that overexpress SNAIL look and act like aggressive cancer cells.
 
Although SNAIL triggers a transformation that helps cells move from the primary tumor to the metastatic site, once the cell arrives at the metastatic site and that tumor starts to grow, SNAIL no longer helps cancer progress. Though becoming softer may help cells spread to the secondary site, they were no longer sturdy enough to form a secondary tumor.
 
The researchers hope that their unique blend of microarray analysis and characterization of physical changes in breast cancer cells undergoing metastasis could aid the search for ways to block or slow the spread of cancer.