Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Research team targets self-cannibalizing cancer cells

12.02.2010
A team of scientists from Princeton University and The Cancer Institute of New Jersey has embarked on a major new project to unravel the secret lives of cancer cells that go dormant and self-cannibalize to survive periods of stress. The work may help produce new cancer therapies to stem changes that render cancer cells dangerous and resistant to treatment.

"We want to know: What role is this self-cannibalization playing in the middle of a tumor?" said team member Hilary Coller, an assistant professor of molecular biology at Princeton. "To treat cancer, it may be that you want to get rid of this ability in tumor cells, so we're searching for inducers and inhibitors of this process."

Eileen White, associate director for basic science at CINJ, Coller and Princeton chemist Joshua Rabinowitz recently received a $1 million National Institutes of Health Challenge Grant through the American Reinvestment and Recovery Act to support the research effort, which is made possible by the longstanding partnership between Princeton and CINJ. The two institutions recently formalized their relationship when Princeton officially joined CINJ as a scientific collaborator to enhance current investigations and foster future work at the frontier of cancer research. CINJ is a Center of Excellence of the University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School and New Jersey's only National Cancer Institute-designated Comprehensive Cancer Center.

For more than 50 years, scientists have known that significant differences exist between the metabolic processes of normal and cancerous cells. These processes encompass the complex set of chemical reactions that control everything from converting food into usable energy to manufacturing cellular components for growth and reproduction. But the causes and consequences of these metabolic differences remain largely unknown -- and the possibilities for exploiting these differences as potential targets for new therapies have been largely untapped. The NIH project is designed to fund inquiry into these important questions.

The altered metabolism of cancer cells allows them to grow rapidly and proliferate, leading to the development of aggressive tumors often able to spread, or metastasize, to other areas of the body. But when subjected to stressful conditions, such as oxygen- and nutrient-deprivation in the center of a tumor or an onslaught of chemotherapeutic agents, these cells are able to stop proliferating and cannibalize portions of themselves, a process known as autophagy.

"This ingenious property allows these cancer cells to tolerate enormous amounts of stress," said White, who also is a professor of molecular biology and biochemistry at Rutgers University. "If they're starving or stressed, they eat themselves and hunker down until the stress is removed. Then, as soon as the stress is gone, they grow back, often killing the patient. If we can understand this process and exploit it for cancer therapy, we may develop new ways to kill the cancer cells without killing the normal cells."

Autophagy is believed to confer stress resistance to cells by providing energy and disposing of old or damaged cell parts that might otherwise prove harmful to the cell over time, and it is not unique to cancer cells: Coller studies a metabolic state known as cellular quiescence in fibroblast cells. Fibroblasts are found in connective tissue, which includes cartilage and the cellular matrix known as stroma that provides support to body structures, such as organs, glands and also tumors. Akin to dormant cancer cells, quiescent fibroblasts take a break from the normal cell growth cycle, but maintain the ability to re-enter the cycle in the future. Like dormant cancer cells, quiescent fibroblasts often engage in autophagy.

Cancer researchers now recognize that a full understanding of how a tumor behaves in response to stress requires knowledge about the metabolism of the cancerous cells and the stromal cells in the tumor, which often constitute a large percentage of the tumor itself, as well as an awareness of how the metabolism of cancerous and noncancerous cells affect one another. Supported by the NIH Challenge Grant, the interdisciplinary team is seeking to define the metabolic networks in stromal and tumor cells, identify the metabolic adaptations that take place as cells transition between different metabolic states, and demonstrate how these changes alter tumor-stromal interaction. The team also is supported by grants from CINJ and the New Jersey Commission on Cancer Research.

The research effort makes use of wide-ranging scientific techniques, including DNA microarray analyses to identify the gene expression changes that underlie metabolic alterations and state-of-the-art methods to identify altered metabolic states by quantifying the concentrations of metabolites -- compounds generated during biological processes that provide chemical clues into which metabolic processes are taking place -- and watching how they change over time.

To do this, the team relies on Rabinowitz's expertise in the use of mass spectrometry to observe the flows, or fluxes, of metabolites that have been labeled with stable isotopic tracers -- nuclei which, like radioactive tracers, have extra neutrons. These tracers are not radioactive, however; instead, they are detected solely based on their different masses.

"If you only take a snapshot of which metabolites are present at any given time, you can miss the bigger picture of what is taking place, especially because many metabolites turn over every few seconds," said Rabinowitz, an associate professor of chemistry and genomics. "Adding isotope-labeled nutrient is the equivalent of determining how fast a stream is moving by adding red food coloring at a given point upstream and seeing how long it takes for the food coloring to make its way downstream."

The project complements clinical trials investigating ways to modulate autophagy in cancer cells, some of which are already under way at CINJ. One study is assessing whether adding hydroxycholoroquine, an anti-malaria drug known to have autophagy-blocking activity, to standard therapy for recurrent colon cancer will increase the number of cancers that go into remission or boost the length of remission.

"The ultimate test will be to take all of our findings and use that information to develop novel approaches for eradicating cancer," White said. "If we can prevent tumor cells from utilizing this altered metabolic state then that should be the Achilles' heel of tumors."

The cutting-edge research effort demonstrates the merits of the collaboration between Princeton and CINJ, which developed through a natural progression driven by science.

"By uniting Princeton's expertise in systems biology, genomics and metabolism with CINJ's top-rate cancer molecular biology and clinical expertise, these collaborations provide opportunities for interaction that promises what the National Cancer Institute has been encouraging – translational research that harnesses basic discoveries for the prevention and treatment of cancer," said James Broach, a Princeton professor of molecular biology who directs the partnership in collaboration with CINJ Deputy Director Edmund Lattime.

"For years our world-class scientists at both facilities have been collaborating on individual cancer research projects," Lattime said. "By entering into a formal partnership, we are strengthening our team science approach so that we can collectively advance cancer research in New Jersey. This will enhance the development of the most innovative, cutting edge cancer treatments for patients in New Jersey and beyond. "

The partnership has already generated groundbreaking results: Last year, a group of Princeton and CINJ researchers led by Princeton molecular biologist Yibin Kang identified a gene, known as Metadherin or MTDH, which is responsible for metastasis and treatment resistance in some 30 to 40 percent of breast cancer patients. The work constituted a breakthrough in the understanding of the disease, laying the groundwork for the development of new treatments, and also established research methods that could be used to identify genes responsible for the metastasis of other types of cancer.

Kitta MacPherson | EurekAlert!
Further information:
http://www.princeton.edu

More articles from Life Sciences:

nachricht How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH

nachricht A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>