Understanding the Transition to Cancer Metastasis – Results of a Battery of Tests on Cancer Cells from Network of Physical Scientists, Engineers, and Cancer Researchers
A team of 95 physicists, engineers, mathematicians, chemists, computational scientists and biologists working on different experiments in 20 US laboratories has gained a new perspective on cancer by pooling their research in a coordinated way. The motivation was to gain insights into the differences between non-malignant and metastatic cancer cells – those that leave the primary tumor and spread to other organs.
Although most aspects of the study have been conducted before, attempts to integrate the results have been hampered by the diversity of samples used. For the first time, a wide range of experiments was conducted simultaneously on the same standardized cells. The results were just published in Nature’s Scientific Reports paper entitled, A physical sciences network characterization of non-tumorigenic and metastatic cells (10.1038/srep01449).
Using two breast cell lines, in which cells are artificially immortalized and bred in laboratories, the scientists focused on the physical changes that accompany the transition of cancer cells to a motile, metastatic form. While metastasis is generally recognized as a critical step in the progression of cancer, there is an incomplete understanding of the physical biology of this transformation. The researchers state that: “Understanding the physical forces that metastatic cells experience and overcome in their microenvironment may improve our ability to target this key step in tumor progression.”
The research was conducted by the network of 12 Physical Sciences-Oncology Centers around the country (PS-OCs), under the auspices of the Office of Physical Sciences-Oncology at the National Cancer Institute. The centers were set up 3 years ago to foster collaboration between physical scientists, biologists and oncologists in order to achieve new insights into cancer.
Laboratories in each center were supplied with identical cell lines and common reagents, and considerable effort was expended to ensure that all the conditions were standardized and documented at regular intervals. This allowed the laboratories to leverage their own expertise and for the results of all the measurements to be integrated across the study.
The number of distinct techniques used to characterize the cells was impressive — more than would be possible in any of the individual labs on their own. One of the lead authors of the paper, Jack (Rory) Staunton, a PhD physics student at Arizona Statue University, comments:
“The work has enabled a comprehensive cataloging and comparison of the physical characteristics of non-malignant and metastatic cells, and the molecular signatures associated with those characteristics. This made it possible to identify unique relationships between observations.”
“We compared the stiffness of normal breast cells and highly metastatic breast cancer cells, and found the cancer cells to be significantly more ‘squishy’ or deformable,” Staunton said. “This makes sense because in order for a cell to metastasize, it has to squeeze through tight passages in the lymphatics and microvasculature, so being squishy helps cancer cells spread through the body.”
Other techniques used included atomic force microscopy, ballistic intracellular nano-rheology, cell surface receptor expression levels, differential interference contrast microscopy, micro-patterning and extracellular matrix secretion, and traction force microscopy.
Staunton, who has been involved in ASU’s PS-OC center since its inception three years ago says the experience has helped his growth as a researcher: “It is the perfect habitat for budding scientists and for trans-disciplinary collaborations.”
Although the cell line exercise involved considerable organization and commitment, it sets a benchmark for future interdisciplinary work in cancer research, and is expected to become the model for future large collaborations.