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How breast cancer cells cooperate to spur tumor growth

Research earns top prize for young scientists

American Association for the Advancement of Science

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WASHINGTON, DC -- Allison Cleary, a cancer research pioneer who demonstrated that subpopulations of breast cancer cells cooperate to enable tumor growth, has been named the 2015 Grand Prize winner of the Science & SciLifeLab Prize for Young Scientists. The prize recognizes promising early-career scientists who conduct groundbreaking life-science research and includes a grand-prize award of US$30,000, supported by Science for Life Laboratory, a coordinated effort among four universities in Sweden and the journal Science, which is published by AAAS, the nonprofit science society.

Significant challenges remain to fight breast cancer; for example, recent studies have revealed that multiple genetically distinct subclones, or tumor cell subpopulations, coexist within individual human breast cancers, which makes them difficult to treat.

While many scientists have thought that this heterogeneity is a consequence of tumor evolution, and that the subclones commonly observed in breast cancers compete with each other within a tumor to be the "fittest," as a graduate student in the laboratory of Dr. Edward Gunther at the Pennsylvania State University College of Medicine, Cleary investigated another possibility--that subclones actually cooperate with each other to promote tumor growth and development.

"We all assume that tumors arise from a single cell--heterogeneity arises through an evolution process--but could it be possible that tumors arise from two separate cells that are interacting with each other? She asks in her grand-prize winning essay, "Teamwork: The Tumor Cell Edition," which will appear in the 4 December 2015 issue of Science.

To explore this question, Cleary and colleagues focused on a mouse model of breast cancer known to produce tumors made of two distinct cell populations; even so, the cells in these tumors have been thought to represent a single clonal population. Using gene sequencing and molecular biology techniques, Cleary and her team showed that these two populations actually represent two genetically distinct subclones: One subclone expresses a cancer-causing gene called Wnt1 and the other subclone has a mutation that activates a different cancer-causing gene called HRas.

After trying a number of strategies, Cleary was able to separate these interwoven tumor cell subclones into individual parts by marking the cells with different fluorescently tagged antibodies and passing them through a cell sorter machine that could recognize the specific wavelengths of the glowing color markers.

She then assessed whether the different subclonal tumor cell populations were capable of re-growing tumors, separately or as a mixture, by transplanting the cells back into the mammary glands of mice. Animals receiving either subclone alone failed to develop tumors, she observed, whereas the cell mixture containing both subclones was highly conducive to tumor formation.

The results demonstrate a "functional codependence" between the distinct tumor cell subclones within these tumors, writes Cleary in her essay. She hypothesizes subclonal heterogeneity is preserved because it may offer a selective advantage. Her work detailing these findings appeared in the 3 April 2014 issue of Nature.

"The results not only raise interesting questions about the nature of tumor progression but may ultimately have implications in the development of new cancer therapies," said Cleary. "It will be very interesting to find out whether these types of cooperative interactions are occurring within human breast tumors. If that is the case, I think there could be an opportunity to develop novel treatments for breast cancer that work to uncouple those cooperative interactions within the tumor."

"Allison Cleary's work was a clear example of a young investigator who became fascinated with a theory that went against the dogma of the field and who designed elegant experiments to determine the reality of the science," said Barbara Jasny, deputy editor of Science.

Cleary, who originally intended to pursue a career as a skeletal muscle physiologist, was drawn to study in Gunther's cancer biology laboratory after she did a rotation in his laboratory. The collaborative environment gave her the freedom to pursue rewarding work, so she changed her career path to study cancer biology. "I was hooked from the very first day--it was seriously like falling down the rabbit hole," said Cleary. "The thing about cancer that I find so interesting is that it's made up of our own cells that have been sort of hijacked and reprogrammed and are now working against us."

Marcia McNutt, Editor-in-Chief of the Science family of journals, further reflected on Cleary's contribution. "Once again in 2015," McNutt said, "the judges were presented with an outstanding slate of candidates whose research is exciting, relevant, and original. While the SciLifeLab Prize may have been conceived to boost the careers of young scientists, it also serves to boost the confidence of all of us that the future of science is in good hands."

Cleary will receive the award for her research in the field of cell and molecular biology in Stockholm, Sweden, on Wednesday, 9 December, during an award ceremony and dinner at the Grand Hôtel in the Hall of Mirrors, which hosted the first Nobel Prize ceremony in 1901.

"I am truly impressed with the awardees' accomplishments and look forward to meeting them in Stockholm soon," said Olli Kallioniemi, Director of SciLifeLab. "After three years the prize is now fully established thanks to the kind support of the Knut and Alice Wallenberg Foundation and we are excited to continue rewarding young scientists in the coming years."

The Science & SciLifeLab Prize for Young Scientists is an annual prize aimed at rewarding young scientists at an early stage of their careers. The categories for this annual award are Cell and Molecular Biology, Ecology and Environment, Genomics and Proteomics, and Translational Medicine.

Cleary, who is completing her M.D., plans to continue studying the role of heterogeneity within breast cancers.

"I am so unbelievably honored to be named one of the winners of the Science and SciLifeLab Prize," said Cleary. "I am excited for the type of exposure that this prize will bring to my research, as well as for the chance to make new connections with other investigators around the world."

Applicants for the 2015 Science & SciLifeLab Prize for Young Scientists submitted a 1000-word essay that was judged by an independent editorial team organized by the journal Science. Their essays were judged on the quality of research and the applicants' ability to articulate how their work would contribute to the scientific field.

The 2015 award also recognizes three runners-up winners, whose essays will be published in the journal Science online at http://www.sciencemag.org/site/feature/data/prizes/scilifelab/. Each of the three runners-up winners will receive US$10,000 and be featured in Science online at http://www.sciencemag.org/site/feature/data/prizes/scilifelab/winning.xhtml.

After the embargo has lifted, follow #ScienceSciLifeLabPrize or #SciLifeLabPrize on Twitter @ScienceMagazine @SciLifeLabPrize @SciPak and Facebook

2015 Grand Prize Winner:

Allison Cleary: For her essay, "Teamwork: The Tumor Cell Edition." Originally from Denver, Colorado, Cleary completed her undergraduate degree in molecular, cellular, and developmental biology at the University of Colorado where she was first introduced to basic science research. From there, she continued her studies at the Pennsylvania State University College of Medicine in their combined M.D./Ph.D. program. While at Penn State, she completed her Ph.D. thesis research in the laboratory of Dr. Edward Gunther, studying mammary gland physiology and breast cancer. She is currently finishing up her M.D. degree and is in the process of applying to Pathology Residency Training Programs on the Physician-Investigator Track.

2015 Runners-up:

Adam Ford: For his essay on the topic of ecology and environment, "The Mechanistic Pathways of Trophic Interactions in Human-Occupied Landscapes." Ford is a wildlife ecologist interested in how predator-prey interactions are shaped by human-modified landscapes. He received a B.Sc. from the University of Victoria (British Columbia), a M.Sc. from Carleton University (Ontario), and his Ph.D. from the University of British Columbia with Assistant Professor Jacob Goheen. Ford is currently a Liber Ero Postdoctoral Fellow in Conservation Science, based at the Department of Integrative Biology at the University of Guelph (Ontario). The research described in his essay sheds new light on the relationships of people, large carnivores, their herbivore prey, and plants in an East African savanna.

Johannes Scheid: For his essay on the topic of translational medicine, "HIV Specific B cell Response in Patients with Broadly Neutralizing Serum Activity." Growing up in New York and Germany in a family of scientists, Scheid was fascinated early in life by the career of a physician scientist. During medical school at the Charité Berlin, he decided to pursue a Ph.D. at The Rockefeller University. In his Ph.D., he investigated the observation that some HIV patients develop very potent antibodies against HIV. The Ph.D. was awarded the 2012 Harold Weintraub award. His work in the laboratory was inspired by interactions with our study participants and he was excited to see some of his work now go into clinical trials. After completing medical school and his Ph.D., he worked for one year as a Clinical Scholar at The Rockefeller University and is now continuing his clinical training at the Massachusetts General Hospital in Boston.

Ludmil Alexandrov: For his essay on the topic of genomics and proteomics, "Understanding the Origins of Human Cancer: Mutational Signatures." Alexandrov is an Oppenheimer Fellow in the Theoretical Biology and Biophysics Group at Los Alamos National Laboratory. He earned his Bachelor of Science degree in Computer Science from Neumont University and received his M.Phil. in Computational Biology as well as his Ph.D. in Cancer Genetics from the University of Cambridge. Alexandrov is a recipient of the 2015 Weintraub Award for Graduate Research and, in 2013, he was listed by Forbes magazine as one of the "30 brightest stars under the age of 30" in the field of science and healthcare. Alexandrov's work is focused on understanding the mutational processes responsible for human cancer and human aging. In 2015, his research was highlighted by the American Society of Clinical Oncology as an important step forward in the fight against cancer.

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About SciLifeLab

SciLifeLab, Science for Life Laboratory, is a Swedish national center for molecular biosciences, with the mission to develop, use and provide advanced technologies for applications in health and environmental research. The center was established in 2010 and became a national resource in 2013, making technologies and expertise available to researchers in all of Sweden and beyond. Today, the center comprises more than 1,200 researchers and personnel. We offer a cross-disciplinary research setting that interacts with healthcare, authorities and industry to meet the need for new clinical methods and a better environment. In addition, SciLifeLab provides education for students and researchers at all levels. SciLifeLab is hosted by four universities; Karolinska Institutet, KTH Royal Institute of Technology, Stockholm University and Uppsala University. The infrastructure is mainly located in Stockholm and Uppsala but we also offer services at other Swedish universities.

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