Clues about how cells become cancerous are revealed in a new catalogue of their physical and chemical features. The catalogue shows, among other things, how malignant cells that break out of tumors and invade other organs are nimbler and more aggressive than non-malignant ones: they are able to pass more easily through small spaces, and they exert a greater force on their environment.
To compile the catalogue, 100 researchers from 20 different centers across the US teamed up to explore the physics and chemistry that shapes the development of cancer cells, a process that is somewhat unclear from a physical science perspective.
The researchers, who belong to the Physical Sciences-Oncology Centers (PS-OC) sponsored by the National Cancer Institute, hope their catalogue will aid the earlier detection of cancerous cells, and even someday help prevent or treat metastatic cancer, that is cancer that has spread and started new tumor sites in other parts of the body, and which is responsible for the vast majority of all cancer deaths.
In a paper published online on 26 April in the journal Scientific Reports, they describe how they carried out a systematic molecular and biophysical comparison between two cell lines, one of metastatic breast cancer cells and the other of non-malignant breast cells, and listed major differences that offer new insights into how cells change from being non-malignant to metastatic.
Robert Austin, professor of physics and leader of the Princeton University PS-OC in New Jersey, says in a statement:
“By bringing together different types of experimental expertise to systematically compare metastatic and nonmetastatic cells, we have advanced our knowledge of how metastasis occurs.”
For instance, they found the two kinds of cell showed differences in in mechanical properties, how they stick to surfaces, how they migrate, respond to oxygen, and produce protein.
Austin and the team in the Princeton PS-OC discovered that even though they travel more slowly than non-malignant cells, metastatic cells travel further and go in a straighter line.
They created an environment made of silicon that simulates the structure of tissue inside the body and observed what happened as the cells made their way through tiny cell-sized chambers and channels etched in the silicon.
Austin says metastatic cells “are essentially jailbreakers”, because they can break through the extracellular matrix, the tough membrane wall that the body creates in an attempt to seal the tumor off from healthy tissue.
Princeton’s physicists and engineers have expertise in microfabrication technology, which is used to make integrated circuits and solar cells. They called on this expertise to make the tiny silicon chambers used in the study.
The Princeton PS-OC also includes teams from the Johns Hopkins University School of Medicine, the Salk Institute for Biological Studies and the University of California-Santa Cruz.
In their paper the researchers also describe how they found metastatic cells recover more quickly from the stress of a low-oxygen environment than do non-malignant cells, confirming results of previous studies.
Many metastatic cells do perish when oxygen supply is low, but those that survive rebound with great vigour, confirming the view that individual cells play an important role in the spread of cancer.
The Princeton PS-OC also discovered malignant cells make proteins that make them more mobile and able to invade the extracellular matrix and escape the tumor. They discovered this by comparing total protein production with that produced in metastatic cells.
Across all the PS-OC network, the researchers use the same two breast epithelial cell lines: non-tumorigenic MCF-10A and metastatic MDA-MB- 231, commonly used models of cancer metastasis. They also use the same reagents and protocols so that results can be compared.
Their lab methods ranged from taking physical measures of how the cells push on surrounding cells to measuring their gene and protein expression.
Nastaran Zahir Kuhn, program manager for the PS-OC at the National Cancer Institute, says in a statement:
“Roughly 20 techniques were used to study the cell lines, enabling identification of a number of unique relationships between observations.”
For instance, using a technique called atomic force microscopy, the researchers found that metastatic cells seem to be softer than nonmalignant cells, while another approach, called traction force microscopy, indicated they exert more force on their surroundings.
These two properties give important clues about how metastatic cells escape their walled-in tumor prison. These could help them for instance, stick to, migrate on, and remodel the tough extracellular matrix that the body has surrounded the tumor with. But at the same time, being softer, metastatic cells can also squeeze through the small spaces in the membrane.
Kuhn says the aim of the nationwide PS-OC program is to pool the expertise of physicists, engineers, computer scientists, chemists and biologists in helping us better understand cancer, and:
“The results of this study demonstrate the utility of such an approach, particularly when studies are conducted in a standardized manner from the beginning.”
In another intriguing study published in January 2013, researchers exploring the interaction between cells and the extracellular matrix suggest knowing how cells know they aren’t upside down may also help fight cancer.
Written by Catharine Paddock PhD