The USC Physical Sciences in Oncology Center is pleased to announce a major multi-institutional paper (DOI: 10.1038/srep01449) on a broad experimental characterization of metastatic cancer cells, recently published in Nature's Scientific Reports.
The paper demonstrates the power of having a network of physicists, engineers, mathematicians, chemists, computational scientists, and biologists working together. In the work described in the paper, nearly 20 laboratories around the country performed coordinated molecular and biophysical studies of non-malignant and metastatic breast cell lines, in order to learn more about what happens to a cell when it transitions to a metastatic state. 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 transition. 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."
Each laboratory was 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 each laboratory to leverage their own expertise and for the results of all the measurements to be integrated across the study.
The list of techniques utilized for cell characterization is impressive—much more than would be possible in any of the individual labs on their own. In fact, nearly twenty distinct techniques were used, including atomic force microscopy, ballistic intracellular nanorheology, cell surface receptor expression levels, differential interference contrast microscopy, LCMS/MS proteomics, micro-patterning and extracellular matrix secretion, traction force microscopy and wound healing assay, and viability, pH and oxygen stress. These, in turn, enabled a comprehensive cataloging and comparison of the physical characteristics of the non-malignant and metastatic cells, and the molecular signatures associated with those characteristics. This made it possible to identify unique relationships between observations. As one example, the atomic force microscopy data suggested that metastatic cells are softer than non-malignant cells whereas the traction force microscopy data suggested that metastatic cells exert more force on their substrate. These data perhaps suggest that the high force exertion by metastatic cells may allow them to adhere to, migrate on, and remodel the extracellular matrix while their flexibility may allow them to squeeze and maneuver in tight spaces.
Over 95 graduate students, post-doctoral scholars, and professors participated in the project, as part of the Physical Sciences-Oncology Centers Network, sponsored by and under the auspices of the Office of Physical Sciences-Oncology of the National Cancer Institute.