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!
Bare bones: Making bones transparent
27.04.2017 | California Institute of Technology
Link Discovered between Immune System, Brain Structure and Memory
26.04.2017 | Universität Basel
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
27.04.2017 | Life Sciences
27.04.2017 | Physics and Astronomy
27.04.2017 | Earth Sciences