The study, published in the January 26 issue of the journal Cell, shows that what scientists thought were two distinct processes in cells—the cells’ normal development and the cells’ response to dangers such as invading organisms—are actually linked. The researchers, who were also from the Salk Institute for Biological Studies and the La Jolla Institute for Allergy and Immunology, say that the linkage of these two processes may explain why cancer, which is normal growth and development gone awry, can result from chronic inflammation, which is an out-of-control response to danger.
“Although there is plenty of evidence that chronic inflammation can promote cancer, the cause of this relationship is not understood,” said Alexander Hoffmann, an assistant professor of chemistry and biochemistry at U.C. San Diego, who led the study. “We have identified a basic cellular mechanism that we think may be linking chronic inflammation and cancer.”
Cellular defense is a rapid process compared to cellular development, just as a state’s response to terrorist threats is swifter than the construction of new infrastructure. However, in both settings, safeguarding against threats and building structures have certain steps in common and require similar types of workers, or molecules.
Hoffmann referred to the parallel sets of steps in cellular defense and development as “mirror image pathways.” His team showed that these pathways are not distinct from one another because they are linked by a protein called p100. They found that inflammation leads to an increase in p100, but that p100 is also used in certain steps in development. Therefore p100 allows communication between inflammation and development.
A small amount of dialogue between inflammation and development is beneficial, say the researchers, akin to how information from anti-terrorism efforts could be useful to crews building the state’s infrastructure. On the other hand, the constant influence of defense processes on development is detrimental.
“Studies with animals have shown that a little inflammation is necessary for the normal development of the immune system and other organ systems,” explained Hoffmann. “We discovered that the protein p100 provides the cell with a way in which inflammation can influence development. But there can be too much of a good thing. In the case of chronic inflammation, the presence of too much p100 may overactivate the developmental pathway, resulting in cancer.”
In the paper, the researchers propose that thinking of the processes of defense and development as part of a single large system “represents an opportunity for therapeutic intervention.” For example, it might be easier to break the link between inflammation and cancer by targeting the developmental pathway, rather than the inflammation pathway.
“Many of the developmental signals that cells use are sent outside the cell, so they should be easier to block with drugs than inflammation signals, which tend to be confined within cells,” said Hoffmann. “It’s more challenging to design drugs that will enter cells.”
Because the molecules that play a role in the inflammation and development pathways have been extensively studied for many years, the researchers say that it is surprising to find a new molecule that significantly revises scientists’ understanding about the interactions between inflammation and development. They credit their discovery to an approach that combines biochemical techniques and computation.
“Our mathematical model of inflammation and development includes 98 biochemical reactions,” said Soumen Basak, a postdoctoral fellow working with Hoffmann. “ When we ran the model, it predicted that p100 levels would be elevated for a significant period of time when the inflammation pathway was stimulated. We confirmed the prediction using biochemical techniques with cells in the laboratory.”
“ The finding is exciting because it means that p100 provides cells with a memory to inflammatory exposure,” added Basak, who was the first author on the paper.
Also contributing to the study were Hana Kim, Jeffrey D. Kearns, Ellen O’Dea, Shannon L. Werner and Gourisankar Ghosh from U.C. San Diego, Vinay Tergaonkar and Inder M. Verma from the Salk Institute for Biological Studies, and Chris A. Benedict and Carl F. Ware from the La Jolla Institute for Allergy and Immunology.
The study was supported by the National Institutes of Health, the Leukemia and Lymphoma Society of America and the American Heart Association.
Sherry Seethaler | EurekAlert!
New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg
Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz
In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport
Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...
The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.
The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...
Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...
Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".
Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...
13.02.2017 | Event News
10.02.2017 | Event News
09.02.2017 | Event News
24.02.2017 | Life Sciences
24.02.2017 | Life Sciences
24.02.2017 | Trade Fair News