Cancerous tumors may spread by pure chance


July 21, 2014

Study could spur new ways of thinking about metastatic disease

The spreading of a cancerous tumor from one part of the body to another may occur through pure chance instead of key genetic mutations, a new study has shown. Download Full Image

Physicists from Arizona State University and the University of Dundee in Scotland have used a statistical model to show that the formation of a new secondary tumor – commonly known as a metastasis – could just as likely derive from “common” cancer cells that circulate in the bloodstream as from “specialist” cancer cells.

Their results, published in the July 18 IOP Publishing’s journal Physical Biology, could spur new ways of thinking about cancer research, demonstrating that statistical physics may be as fundamental as complex genetics when studying the occurrence and treatment of metastatic disease.

In the conventional view of metastasis, only certain “specialist” cancer cells from the primary tumor can successfully metastasise. These cells have been compared to decathletes due to their ability to perform a number of different tasks, such as invade local tissue, enter, survive in and leave the bloodstream, and colonise new tissue environments.

This view explains the inefficiency of metastasis and why it often takes years to cause death in most patients – it is highly improbable that a cell would possess all of the genetic mutations required to carry out all of the above functions.

In their study, Luis Cisneros, post-doctoral research associate in ASU’s BEYOND Center, and Timothy Newman, professor of biophysics at the University of Dundee, also considered the possibility that a large number of “common” cancer cells that are free flowing in the bloodstream may, on very rare occasions, cause metastasis by pure chance.

“If we use a military metaphor, a key mission can be accomplished using either a handful of highly trained special forces – in this case the specialist cells – or a huge number of untrained infantry – the common cancer cells – in which case, a handful of ordinary soldiers will, by sheer luck, be successful,” Newman said. “If one could magically observe the early growth of a metastasis, we show there would be no way of telling from the growth dynamics whether the tumor was seeded by a special forces cell or a lucky infantryman.”

The researchers used methods from statistical physics and probability theory to calculate the probability of such rare events caused by common cancer cells and the timescales of how fast these events could occur. They found that successful metastatic growth from common cells, although rare, would proceed extremely rapidly, and appear deterministic.

In particular, their results showed that in the early stages of metastatic growth, the growth of a new colony of cancer cells formed by a specialist cell with just the right amount of mutations was statistically indistinguishable from a colony that formed from a common cell which happened to "get lucky."

“If we allow ourselves to consider the role of randomness, then we open the door to perceiving surprising effects of the statistical fluctuations that may not be expected by naïve reasoning,” Cisneros said.

The researchers also used very crude physiological data to estimate that the rare events caused by common cells would lead to semi-stable metastases in the size range of about 50 cells, which was striking as metastases of this size have been previously observed in experiments on mice and zebrafish.

Such tiny metastases would be too small to observe using medical imaging in human patients, but could possibly be found through fine examination of biopsied tissue, which the researchers are looking to investigate in future studies.

The published version of the paper ‘Quantifying metastatic inefficiency: rare genotypes versus rare dynamics’ (Cisneros L H and Newman T J 2014 Phys. Biol 11 046003) is available online at http://iopscience.iop.org/1478-3975/11/4/046003/article.

Sharon Keeler

ASU professor's lab provides pipeline to medical school


July 22, 2014

There’s no guarantee that undergraduate students who conduct research in the lab of Arizona State University professor Peter Jurutka will have an advantage if they decide to apply for admission to medical school. But based on Jurutka’s track record, working under his guidance certainly doesn’t seem to hurt.

Of the 80 students accepted for 2012 admission to the University of Arizona College of Medicine – Phoenix, four were recent ASU graduates who participated in research projects in Jurutka’s lab on ASU’s West campus. That’s a full five percent of admitted students. All four are now third-year medical students at the U of A. Shane Batie Download Full Image

Jurutka is an associate professor in ASU’s New College of Interdisciplinary Arts and Sciences, the core college on the West campus. He researches a variety of health-related biochemical topics, with a focus on vitamin D, nutrition and cancer.

“Much of the research in my lab is driven by undergraduate students,” Jurutka said. “They value the opportunity to become involved in a meaningful research experience.”

Dozens of students have worked with Jurutka during his decade at ASU. Their work regularly results in their becoming co-authors of papers published in refereed academic journals and presented at national conferences.

Jurutka’s reputation has spread beyond the West campus; students from other ASU campuses also seek him out as a mentor.

“Working with Dr. Jurutka really prepared me for the challenges of applying to and succeeding in medical school,” said Rimpi Saini, one of the four of Jurutka’s mentees recently admitted to the U of A College of Medicine – Phoenix. She received a bachelor's degree in molecular biology/biotechnology and psychology from the College of Liberal Arts and Sciences on ASU’s Tempe campus.

“I quickly learned how to be organized, efficient and thorough in my work,” Saini said about her research experience with Jurutka. “I also learned valuable public speaking skills, as I had to present my research data in weekly lab meetings and occasional conferences. When it was time to apply for medical school, I knew that Dr. Jurutka would serve as an excellent mentor throughout the process.”

Shane Batie echoed Saini’s comments about the value of Jurutka’s mentorship. “He served as a mentor, teacher, professor and guidance counselor,” said Batie, who earned his bachelor’s degree in life sciences on the West campus through New College’s School of Mathematical and Natural Sciences.

“Dr. Jurutka demands excellence from his students, which drives us to work hard and be productive,” Batie said. “We had weekly meetings to discuss experiments, results and work on manuscripts to submit for publication. I consider the work I did with Dr. Jurutka the most beneficial piece of my application for medical school. He also reviewed and provided critique for my personal statement, a two-page essay that accompanies the medical school application.”

“Peter’s dedication to student success is typical for our faculty members,” said Roger Berger, director of the School of Mathematical and Natural Sciences. “Whether students aspire to medical school, scientific research or a career path related to computing, math or statistics, our professors work tirelessly to help them reach their goals.”

“Dr. Jurutka cares for each and every one of his students, and his mentorship and direction really helped guide me in my journey to get into medical school,” said Iza Aguayo, another student who commuted to work with Jurutka and now is at the U of A. She earned a biological sciences degree from ASU’s College of Liberal Arts and Sciences. “Living in the East Valley, I had to travel a great distance in order to be able to work in his lab several days a week. But I would do it again in a heartbeat.”

Jurutka said that the West campus offers students a tremendous opportunity for research and provides an environment that fosters direct student interaction with faculty, an attribute that leads to greater involvement in independent research. “New College has a robust research program, and students who are motivated to work hard can become significant players in conducting and publishing cutting-edge research,” he said.

“To this day, Dr. Jurutka is still one of my most valuable mentors,” Saini said. “I always feel very comfortable emailing him with any questions I have about my future career, as he always offers valuable, unbiased advice. I attribute much of my success to the skills learned from him and the research experience.”

Jurutka teaches such subjects as applied molecular genetics and genomics, chemistry and biochemistry, as well as individualized lab instruction and undergraduate research. He has received a number of prestigious honors, including the ASU Faculty Achievement Award in 2011 for Excellence in Undergraduate Student Mentoring; the Norwich-Eaton Young Investigator Research Award for significant contributions to the field of bone and mineral research; and the John Haddad Young Investigator Award presented by Advances in Mineral Metabolism and the American Society of Bone and Mineral Research. Jurutka is also an independent reviewer for several professional journals.

The University of Arizona College of Medicine – Phoenix is a full, four-year program based in downtown Phoenix focused on training individuals to become exemplary physicians, scientists and leaders. The college offers students a varied experience working with clinical partners, including Banner Health, Phoenix Children’s Hospital, Maricopa Integrated Health System, St. Joseph’s Hospital and Medical Center, Scottsdale Healthcare, Phoenix Baptist, Mayo Clinic and the Phoenix VA Health Care System.