Physicists, biologists unite to expose how cancer spreads

April 26, 2013 by Catherine Zandonella
A multi-institutional study including researchers from Princeton University's Physical Sciences-Oncology Center found that metastatic cancer cells are more aggressive and nimble than nonmalignant cells. The Princeton group used silicon-etched microchannels (above) to study the behavior and physical properties of cancer cells. In this device, metastatic cancer cells enter the narrow channels at one end and accelerate as they rapidly move down the channel. Such high motility is a hallmark of metastasis and also indicative of high glucose metabolism, another hallmark of cancer. Credit: Guillaume Lambert

(Medical Xpress)—Cancer cells that can break out of a tumor and invade other organs are more aggressive and nimble than nonmalignant cells, according to a new multi-institutional nationwide study. These cells exert greater force on their environment and can more easily maneuver small spaces.

The researchers report in the journal Scientific Reports that a systematic comparison of metastatic cells to healthy revealed dramatic differences between the two cell lines in their mechanics, migration, oxygen response, and ability to stick to surfaces. The researchers discovered new insights into how cells make the transition from nonmalignant to metastatic, a process that is not well understood.

The resulting catalogue of differences could someday help researchers detect earlier and someday prevent or treat metastatic cancer, which is responsible for 90 percent of all cancer deaths, according to the study. It was conducted by a network of 12 federally funded Physical Sciences-Oncology Centers (PS-OC) sponsored by the National Cancer Institute. PS-OC is a collaboration of researchers in the physical and biological sciences seeking a better understanding of the physical and chemical forces that shape the emergence and behavior of cancer.

"By bringing together different types of experimental expertise to systematically compare metastatic and nonmetastatic cells, we have advanced our knowledge of how metastasis occurs," said Robert Austin, professor of physics and leader of the Princeton PS-OC, along with senior co-investigator Thea Tlsty of the University of California-San Francisco.

Researchers with the Princeton PS-OC, for instance, determined that metastatic cells, in spite of moving more slowly than nonmalignant cells, move farther and in a straighter line, Austin said. The investigators studied the cells' behavior in tiny cell-sized chambers and channels etched out of silicon and designed to mimic the natural environment of the body's interior.

"The mobility of these metastatic cells is an essential feature of their ability to break through the tough membrane [the extracellular matrix] that the body uses to wall off the tumor from the rest of the body," Austin said. "These cells are essentially jail-breakers."

The tiny silicon chambers were built using Princeton's expertise in microfabrication technology—typically used to create small technologies such as integrated circuits and solar cells—and are an example of the type of expertise that physicists and engineers can bring to cancer research, Austin said. For the current study, the Princeton team included physics graduate students David Liao and Guillaume Lambert, and postdoctoral researchers Liyu Liu and Saurabh Vyawahare. They worked closely with a research group led by James Sturm, Princeton's William and Edna Macaleer Professor of Engineering and Applied Science and director of the Princeton Institute for the Science and Technology of Materials (PRISM) where the microfabrication was done.

The Princeton PS-OC also includes collaborators at the Johns Hopkins University School of Medicine, the Salk Institute for Biological Studies and the University of California-Santa Cruz.

The nationwide PS-OC program aims to crack the difficulty of understanding and treating cancer by bringing in researchers from physics, engineering, computer science and chemistry, said Nastaran Zahir Kuhn, program manager for the PS-OC at the .

Other notable findings from the paper include that metastatic cells recover more rapidly from the stress of a low-oxygen environment than nonmetastatic cells, which is consistent with previous studies. Although the low-oxygen environment did kill many of the metastatic cells, the survivors rebounded vigorously, underscoring the likely role of individual cells in the spread of cancer. The study also looked at total protein production and detected proteins in the metastatic cells that are consistent with the physical properties such as mobility that malignant cells need to invade the extracellular matrix.

"The PS-OC program aims to bring physical sciences tools and perspectives into cancer research," Kuhn said. "The results of this study demonstrate the utility of such an approach, particularly when studies are conducted in a standardized manner from the beginning."

For the nationwide project, nearly 100 investigators from 20 institutions and laboratories conducted their experiments using the same two cell lines, reagents and protocols to assure that results could be compared. The experimental methods ranged from physical measurements of how the cells push on surrounding cells to measurements of gene and protein expression.

"Roughly 20 techniques were used to study the cell lines, enabling identification of a number of unique relationships between observations," Kuhn said.

For example, a technique known as atomic force microscopy indicated that metastatic cells are softer than nonmalignant cells whereas a different technique, traction force microscopy, suggested that metastatic exert more force on their surroundings, Kuhn said. Together these two findings may indicate that can exert force to stick to, migrate on and remodel the tough extracellular matrix that surrounds the tumor, while remaining flexible enough to squeeze through small spaces in that membrane.

Explore further: Battery of tests on cancer cells shows them as 'squishy,' yet tactically strong

More information: www.nature.com/srep/2013/13042 … /full/srep01449.html

Related Stories

Battery of tests on cancer cells shows them as 'squishy,' yet tactically strong

April 26, 2013
A team of student researchers and their professors from 20 laboratories around the country have gotten a new view of cancer cells. The work could shed light on the transforming physical properties of these cells as they metastasize, ...

Squeezing ovarian cancer cells to predict metastatic potential

October 10, 2012
(Medical Xpress)—New Georgia Tech research shows that cell stiffness could be a valuable clue for doctors as they search for and treat cancerous cells before they're able to spread. The findings, which are published in ...

Researchers discover protein that may control the spread of cancer

February 26, 2013
Researchers at the University of Hawai'i Cancer Center have uncovered a novel mechanism that may lead to more selective ways to stop cancer cells from spreading. Associate Professor Joe W. Ramos PhD, a cancer biologist at ...

Fighting melanoma's attraction to the brain

September 19, 2012
(Medical Xpress)—The process of metastasis, by which cancer cells travel from a tumor site and proliferate at other sites in the body, is a serious threat to cancer patients. According to the National Cancer Institute, ...

Scientists identify new mechanism of prostate cancer cell metabolism

March 22, 2012
Cancer cell metabolism may present a new target for therapy as scientists have uncovered a possible gene that leads to greater growth of prostate cancer cells.

Recommended for you

Researchers release first draft of a genome-wide cancer 'dependency map'

July 27, 2017
In one of the largest efforts to build a comprehensive catalog of genetic vulnerabilities in cancer, researchers from the Broad Institute of MIT and Harvard and Dana-Farber Cancer Institute have identified more than 760 genes ...

Cancer-death button gets jammed by gut bacterium

July 27, 2017
Researchers at Michigan Medicine and in China showed that a type of bacterium is associated with the recurrence of colorectal cancer and poor outcomes. They found that Fusobacterium nucleatum in the gut can stop chemotherapy ...

Long-sought mechanism of metastasis is discovered in pancreatic cancer

July 27, 2017
Cells, just like people, have memories. They retain molecular markers that at the beginning of their existence helped guide their development. Cells that become cancerous may be making use of these early memories to power ...

Manmade peptides reduce breast cancer's spread

July 27, 2017
Manmade peptides that directly disrupt the inner workings of a gene known to support cancer's spread significantly reduce metastasis in a mouse model of breast cancer, scientists say.

Blocking the back-door that cancer cells use to escape death by radiotherapy

July 27, 2017
A natural healing mechanism of the body may be reducing the efficiency of radiotherapy in breast cancer patients, according to a new study.

Glowing tumor technology helps surgeons remove hidden cancer cells

July 27, 2017
Surgeons were able to identify and remove a greater number of cancerous nodules from lung cancer patients when combining intraoperative molecular imaging (IMI) - through the use of a contrast agent that makes tumor cells ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.