Network of scientists reports 'squishy' cells in new cancer research paper

April 26, 2013

A team of student researchers and their professors from 20 laboratories around the country is seeing a new view of cancer cells.

The work could shed light on the transforming physical properties of these cells as they metastasize, said Jack R. Staunton, a doctoral candidate at Arizona State University in the lab of professor Robert Ros, from the Department of Physics, and the lead author of a paper reporting on the topic. Download Full Image

Metastasis is a critical step in the progression of cancer – a period when the cancer spreads from one organ, or part, to another. While much is known about metastasis, there remains an incomplete understanding of the physical biology of the transition. To bridge the gap in understanding, more than 95 graduate students, postdocs and professors in a variety of laboratories across the United States subjected two cell lines to a battery of high-tech tests and measurements.

Their results, outlined in the paper “A physical sciences network characterization of non-tumorigenic and metastatic cells,” were published April 26 in Scientific Reports.

The researchers performed coordinated molecular and biophysical studies of non-malignant and metastatic breast cell lines to learn more about what happens to a cell when it transitions to a metastatic state.

Each laboratory is part of the National Cancer Institute’s Physical Sciences Oncology Center (PSOC), a network of 12 centers devoted to understanding the physical sciences of cancer. ASU’s center, the Center for the Convergence of Physical Science and Cancer Biology, is led by professor Paul Davies.

Each PSOC was supplied with identical cell lines and common reagents, and considerable effort was made to ensure that all the conditions were standardized and documented at regular intervals. Staunton said the ASU group made three contributions to the study.

Other ASU researchers involved in the project and co-authors on the paper include Alexander Fuhrmann, Vivek Nandakumar, Laimonas Kelbauskas, Patti Senechal, Courtney Hemphill, Shashanka Ashili, Roger H. Johnson and Deirdre Meldrum.

“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.”

Taken together, researchers at the 12 PSOCs used some 20 distinct techniques, including 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.

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, Staunton said.

“We were surprised that even though the cancer cells are softer, they are able to exert more contractile forces on the fibers surrounding them, which was determined at the Cornell University PSOC by a method called traction force microscopy. This pair of characteristics is somewhat contradictory from a purely physical perspective, but it makes sense for a cancer cell, since both traits improve their chances of metastasizing. Understanding why is still an active area of research,” explained Staunton, who is working towards his doctorate in physics.

“Another interesting finding was that a protein called CD44, which doubles as a cancer stem cell marker and as a molecule that helps the cell stick to certain fibers in the extracellular matrix, is equally abundant in the normal and cancer cells," he added. "But in the cancer cells the proteins don’t make it to the cell surface.

“For some reason they stay inside the cytoplasm, so the cancer cells are not as sticky. This is another trait that contributes to their ability to spread through the body.”

The PSOC network went to great lengths to have all of the studies performed under comparable conditions. While the cell lines studied are well understood, part of the effort for the network was to prove they could consistently coordinate the research.

Staunton, who has been involved in ASU’s center since its inception, says the experience has helped his growth as a researcher.

“It is the perfect habitat for budding scientists and for transdisciplinary collaborations,” he said.

Associate Director, Media Relations & Strategic Communications


Global health grad studies changing body image perceptions

April 26, 2013

When Isa Rodriguez-Soto began her global health doctoral program at ASU in 2008, she wasn’t exactly sure what "global health" as a concept meant. But she wanted to investigate issues of health regarding body size and knew that she’d come to the right place to do that.

“I talked about this with a faculty member, who mentioned that Puerto Ricans value ‘plump’ women,” says Rodriguez-Soto. “That bit of information from scientific literature had not been my experience growing up in Puerto Rico. This apparent incongruence between the scientific literature and my own experience slowly but surely became my research question.” Download Full Image

It turns out that the research cited by the professor had been conducted three decades ago. This sparked Rodriguez-Soto’s interest in understanding how and why culture changes in relation to body ideals.

Under the direction of medical anthropologist Jonathan Maupin, she used an intergenerational approach and discovered that Puerto Ricans find it acceptable to gain weight with aging, during a divorce or postpartum. Thin bodies are associated with beauty and health, and healthy women who don’t resemble the thin ideal submit themselves to dangerous weight loss practices to achieve social and self-acceptance.

“Weight discrimination and concern about being overweight were evident in Puerto Rican everyday life, indicated by the role of media and acculturation in this study,” she says. “In short, the positive valuation of fat in the Puerto Rican cultural body size model of the 1970s has shifted toward a negative valuation of fat and a preference for thin body size.”

Rodriguez-Soto admits, “When I started framing my research, in light of the global trends regarding body image, was when I really started understanding the ‘global’ in global health.”

She explains that, in our increasingly interconnected world, understanding shifts in cultural norms and ideals is important, as is documenting the changes themselves, along with the mechanisms that drive them.

“For example, in my research, based on scientific literature, we would expect media from the U.S. to be a major influence on body norms,” she says. “Interestingly, the media Puerto Ricans reported being associated with a thin body ideal were Latin American television shows.”

With recent research showing that fat stigma is now worldwide, Rodriguez-Soto realizes that her work is as timely as it is significant.

“The body is one of the primary ways through which we experience our daily lives," she says. "How we feel about it, how particular bodies are valued or conceptualized in society, has a direct impact on how we view ourselves.”

“Isa represents the philosophy and scope of the global health program in the School of Human Evolution and Social Change, integrating in-depth ethnographic research with empirical data to examine the dynamic interplay between culture and biology," says Maupin. "Her work is theoretically and methodologically innovative and makes a significant contribution not only to studies of body image, but also larger issues of cultural stability and change.”

Before coming to ASU’s College of Liberal Arts and Sciences, Rodriguez-Soto received a bachelor’s degree in biology from the University of Puerto Rico in her hometown of Mayagüez and a master’s in anthropology from the University of Colorado at Boulder.

She will graduate this May and assume a tenure-track position as an assistant professor in the Department of Anthropology and Classical Studies at the University of Akron in Ohio in the fall.

She plans to continue exploring body size models with ethnic minorities in the United States, as well as her research in Puerto Rico by examining the emerging issue of weight discrimination and assessing nutrition, food access and food perceptions on the western main island.

Rebecca Howe

Communications Specialist, School of Human Evolution and Social Change