A collaborative study from about 100 researchers in 20 U.S. institutes published in the journal Scientific Reports, revealed the biophysical properties of metastatic breast cancer cells, the cells with the ability to migrate from the initial tumor, degrade the surrounding matrix, squeeze through small pores and migrate via blood circulation to distant sites in our body in order to start secondary tumors.
Researchers around the globe are investigating the environmental, genetic and molecular factors that transform a normal cell into a cancer cell and later into a metastatic cancer cell. These are the cells which will eventually kill the patient.
All cells in our body are subjected to physical forces; they are compressed and they are attached to each other or to the surrounding matrix. Our tissue homeostasis is dependent on that. However, the tumor cells can sustain increased forces by the surrounding tissues and later leave from the primary site and migrate through very small pores or degrade the surrounding matrix, a process called metastasis. Most of the times they can survive in areas with extreme conditions, such as low oxygen, no growth factors or low pH. This extreme fitness of cancer cells is usually overlooked and the physical changes are not known yet.
But the physical characteristics of these cells might be equally influential as the genetic and molecular changes. “From a clinical perspective, it is not at all unimaginable that there is a connection between the mechanics of tumours and their underlying biology,” said to Nature some time ago, physicist and graduate student Jan T. Liphardt of the University of California, Berkeley, who participated in the study.
Liphard is a member of the Physical Sciences–Oncology Centers (PS-OC) Network, a multi-disciplinary network of twelve research centers across the US, whose goal is to study cancer from a physical sciences perspective. These research groups used normal breast cells and metastatic breast cancer cells and subjected them to physical, biochemical, and molecular assays. In the end they compared their biophysical abilities. The experiments seemed like putting a medium-trained individual and an Olympic champion in the gym and comparing their performance.
Initially, the results showed that cancer cells have different architecture of their nucleus, which is believed to affect expression of genes. They also found that cancer cells proliferate normally irrespective of the degree of stiffness of the surrounding matrix, an ability apparently important for a cell that moves between areas in the body with varying rigidity.
Furthermore, cancer cells restrict CD44, an adhesion molecule normally found on the cell membrane, in the interior of the cell and not on the outer membrane. This way cancer cells do not attach very well, thus they can move more freely.
Next, the research groups compared how cells migrate and they found that, despite the cancer cells moving slower, they move further from the primary site and in a straighter line without any restriction in the distance traveled. “These cells are essentially jail-breakers,” Robert H. Austin, professor of Physics in Princeton University and leader of the Princeton PS-OC, said.
Cancer cells were also more elastic and able to both withstand and exert higher mechanical forces from and to their environment due to their softer cytoskeleton, the protein filaments which work as scaffold of all cells. Lastly, cancer cells were able to recover quickly and live normally in hypoxic or acidic (low pH) environments.
Collectively, the results showed that the cancer cells are like John McClane in Die Hard movies.
This is the first time that the superpowers of a cancer cell have been systematically decoded and compared to a normal cell. And it is a demonstration of what physicists, engineers, chemists, computer scientists and cancer researchers can do if they combine forces. Could such techniques of the physical sciences be applied to study cancer in vivo? The authors think that this is possible for most of the techniques used in this study.
As the authors stated: “This pilot study validates the laboratory network approach and the use of physical sciences techniques to investigate cancer cell biology”.