Using a "systems biology" approach – which focuses on understanding the complex relationships between biological systems – to look under the hood of an aggressive form of breast cancer, researchers for the first time have identified a set of proteins in the blood that change in abundance long before the cancer is clinically detectable. The findings, by co-authors Christopher Kemp, Ph.D., and Samir Hanash, M.D., Ph.D., members of Fred Hutchinson Cancer Research Center's Human Biology and Public Health Sciences divisions, respectively, are published online ahead of the Aug. 1 print issue of Cancer Research.
Studying a mouse model of HER2-positive breast cancer (cancer that tests positive for a protein called human epidermal growth factor receptor 2) at various stages of tumor development and remission, the researchers found that even at the very earliest stages the incipient tumor cells communicate to normal tissues of the host by sending out signals and recruiting cells, while the host tissues in turn respond to and amplify the signals.
"It is really a 'systems biology' study of cancer, in that we simultaneously examined many genes and proteins over time – not just in the tumor but in blood and host tissues." Kemp said. "The overall surprising thing we found was the degree to which the host responds to cancer early in the course of disease progression, and the extent of that response. While a mouse – or presumably a human – with early-stage cancer may appear normal, our study shows that there are many changes occurring long before the disease can be detected clinically. This gives us hope that we should be able to identify those changes and use them as early detection tools with the ultimate goal of more effective intervention."
Traditionally, it has been thought that tumor cells shed telltale proteins into the blood or elicit an immune response that can lead to changes in blood-protein levels. "What is new here is that the predominant protein signals we see in blood originate from complex interactions and crosstalk between the tumor cells and the local host microenvironment," Kemp said.
Until now, such tumor/host interactions have been primarily studied one gene at a time locally, within the tumor; this is the first study to monitor the systemic response to cancer in a preclinical tumor model, tracking the abundance of cancer-related proteins throughout tumor induction, growth, and regression. Of approximately 500 proteins detected, up to a third changed in abundance; the number increased with cancer growth and decreased with tumor regression.
"We found a treasure trove of proteins that are involved in a variety of mechanisms related to cancer development, from the formation of blood vessels that feed tumors to signatures of early cancer spread, or metastasis," Kemp said.
Proteins associated with wound repair were most prevalent during the earliest stages of cancer growth, which could point to a potential target for early cancer detection. "Rather than blindly search for cancer biomarkers, an approach based on comprehensive understanding of the systems biology of the disease process is likely to increase the chances to identify blood-based biomarkers that will work in the clinic," Kemp said.
The next steps will involve selecting the most promising protein candidates found in mice and determining whether the same circulating proteins are markers of early breast cancer development in humans, with the ultimate goal of designing a blood test for earlier breast cancer detection.
The Paul G. Allen Family Foundation, the National Cancer Institute Mouse Models of Human Cancer Consortium and the Canary Foundation funded the research.
At Fred Hutchinson Cancer Research Center, our interdisciplinary teams of world-renowned scientists and humanitarians work together to prevent, diagnose and treat cancer, HIV/AIDS and other diseases. Our researchers, including three Nobel laureates, bring a relentless pursuit and passion for health, knowledge and hope to their work and to the world. For more information, please visit fhcrc.org.
Kristen Woodward | EurekAlert!
How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH
A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)
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...
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...
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...
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...
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)...
19.06.2017 | Event News
13.06.2017 | Event News
13.06.2017 | Event News
23.06.2017 | Physics and Astronomy
23.06.2017 | Physics and Astronomy
23.06.2017 | Information Technology