Blood-clotting protein linked to cancer and septicemia

Featured In: Disease Research

By EurekAlert Friday, February 4, 2024

newsvine diigo google
slashdot
Share
Loading...

In our not-so-distant evolutionary past, stress often meant imminent danger, and the risk of blood loss, so part of our body's stress response is to stock-pile blood-clotting factors. Scientists in the Molecular Medicine Partnership Unit (MMPU), a collaboration between the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, and the University of Heidelberg Medical Centre, have discovered how stressed cells boost the production of the key blood-clotting factor, thrombin. Their work, published today in Molecular Cell, shows how cancer cells may be taking advantage of this process, and opens new possibilities for fighting back, not only against cancer but also against septicaemia, where increased blood clotting is still one of the leading causes of death.

Blood clots tend to form more often in the veins of people with cancer, a syndrome first described almost 150 years ago by French physician Armand Trousseau. In recent years, doctors have also come to realise that people with activated blood coagulation are more likely to develop cancer. Accordingly, recent studies have shown that anti-coagulants may help treat and prevent cancer, but exactly how blood-clotting and cancer progression are linked was unclear – until now.

"For the 1st time, we have something in hand that might explain this enigmatic relationship between enhanced pro-coagulatory activities and the outcome of cancer," says Sven Danckwardt, who carried out the research within the MMPU.

The amount of thrombin our cells produce is controlled by two sets of proteins: proteins that slow thrombin production, and proteins that speed it up. Both types of protein act by binding to the cellular machinery that synthesises thrombin, and, under normal conditions, the production-slowing proteins keep thrombin levels low. But Danckwardt and colleagues discovered that, when our cells come under stress from inflammation, another protein, called p38 MAPK, reacts by adding a chemical tag to those production-slowing proteins. That tag makes it harder for the production-slowing proteins to bind to the thrombin-synthesising machinery, allowing the proteins that speed up production to take over. So inflammation caused by cancer could lead to increased thrombin levels and, as thrombin is a blood-clotting agent, this could explain why cancer patients are more likely to suffer from blood-clots. The scientists believe this new mechanism of gene regulation may apply to other genes, too.

"Knowing the exact molecules involved, and how they act, has implications for treatment, especially as drugs that inhibit p38 MAPK are already being tested in clinical studies for other conditions," says Matthias Hentze, Associate Director of EMBL and co-director of MMPU, adding: "those drugs could be good candidates for potential cancer or septicaemia therapies."

The Heidelberg scientists found that p38 MAPK also influences thrombin production during septicaemia. Also known as blood poisoning, septicaemia occurs when bacteria or other pathogens enter the bloodstream, leading to widespread infection and to blood-clotting problems. When they analysed liver samples taken from septicaemic mice and from cancer patients, the scientists discovered that thrombin production increases in response both to widespread inflammation during septicaemia and to localized inflammation at the tumour's invasion front, where cancer cells are spreading into nearby tissue.

Aside from its role as a blood-clotting agent, thrombin is also involved in creating new blood vessels, and it is able to degrade the extracellular matrix that keeps cells together. So it's possible that the cancer cells are increasing thrombin production to help the tumour spread, by making it easier to invade healthy tissue and creating blood vessels to supply the new tumour cells. This, the researchers believe, could explain why people with blood-clotting problems seem to have a higher risk of developing cancer.

"This study shows the benefits of partnerships like the MMPU, which bridge the gap between clinical and basic research," Andreas Kulozik from the University of Heidelberg Medical Centre, co-director of MMPU, concludes.

SOURCE

Join the Discussion
Rate Article: Average 5 out of 5
register or log in to comment on this article!

0 Comments

Add Comment

Text Only 2000 character limit

Page 1 of 1

Research Exchange

Bringing the Cell Image into Focus

Nov 2 2010

Improvements in transmission electron microscope (TEM) technology increase the power of this imaging tool for the study of cell biology.

Finding a Cure for Spinal Cord Injury with On-Demand LIMS

Oct 25 2010

The Miami Project to Cure Paralysis finds an on-demand laboratory information management system (LIMS) helps to accelerate discovery in its HCS projects.

Saving Cells: Image Processing for Improved Viability, Part II: Iterative Deconvolution

Oct 25 2010

3D light microscopy and deconvolution provide a means to investigate 3D structure, providing near-confocal quality images without the temporal requirements or potentially damaging phototoxicity associated with other 3D imaging technologies. This article is Part II in a series regarding viability, resolution improvement, and measurement in fluorescence imaging. Part I focused on spectral unmixing.

Saving Cells: Image Processing for Improved Viability

Sep 22 2010

This article is Part I of a two-part series regarding viability, resolution improvement, and measurement in fluorescence imaging. Part II will focus on deconvolution.

Production of Recombinant Proteins and Monoclonal Antibodies in Hollow Fiber Bioreactors

Jan 25

While well-understood, robust and convenient, classical batch-style 2-D culture on non-porous supports or 3-D suspension culture in other devices are really not very biologically relevant models. Cell culture conditions can affect the quality of the antibody or protein produced.

Selecting Robots for Use in Drug Discovery and Testing

Dec 6 2010

Drug discovery and testing, with their need for speed, repeatability and verification, are ideally suited to benefit from robot automation. It is therefore not surprising that robots have been at the forefront of automation developments in both these areas.

HP Scalable Network Storage Systems for Life Sciences

Sep 13 2010

Life sciences research today is advancing exponentially, each step bringing us closer to the realization of truly personalized medicine–preventive care and treatments designed specifically for each individual. In the near future, PCPGM healthcare researchers expect to be able to use predictive genetic testing to create custom treatment plans for individuals and deliver dramatic improvements over today’s one-size-fits-all approach. But research capabilities are only part of the equation; current storage and operating capacities must also evolve to accommodate ever-expanding amounts of data before the goal of personalized medicine can be realized.

Step up to the MIQE

Mar 30 2010

Over the years, polymerase chain reaction (PCR) has evolved into a readily automated, high throughput quantitative technology. Real-time quantitative PCR (qPCR) has become the industry standard for the detection and quantification of nucleic acids for multiple application, including quantification of RNA levels. But a lack of consensus among researchers on how to best perform and interpret qPCR experiments presents a major hurdle for advancement of the technology. This problem is exacerbated by insufficient experimental detail in published work, which impedes the ability of others to accurately evaluate or replicate reported results.

Using the Tecan Genesis Workstation to Automate a Cytometric Bead Array (CBA) Immunoassay

Mar 11 2010

The poster describe the process involved in automating a Cytometric Bead Array (CBA) immunoassay developed to measure relative concentrations of serum antibodies against Tetanus (TT), Sperm Whale Myoglobin (SWM) and Keyhole Limpet Hemocyanin (KLH) in KLH-immunized volunteers.

Ensuring Quality in Assays Performed with Automated Liquid Handlers

Feb 2 2010

The focus of this presentation is to highlight the need of ensuring quality in important assays performed with automated liquid handlers. Nearly all assays performed within a laboratory are volume-dependent. In turn, all concentrations of biological and chemical components in these assays, as well as the associated dilution protocols, are volume-dependent. Because analyte concentration is volume-dependent, an assay’s results might be falsely interpreted if liquid handler variability and inaccuracies are unknown or if the system(s) go unchecked for a long period.

Inkjet System for Protein Crystallography

Feb 1 2010

X-ray crystallography is used routinely by scientists to obtain the three dimensional structure of a biological molecule of interest.Such information can be used to determine how a pharmaceutical interacts with a protein target and what changes might improve functionality. However, the crystallization of macromolecules still remains a serious hindrance in structural determination despite impressive advances in screening methods and technologies.

Attention Deficit & Hyperactivity in a Drosophila Memory Mutant

Attention Deficit & Hyperactivity in a Drosophila Memory Mutant

Nov 9 2009

Action selection is modulated by external stimuli either directly or via memory retrieval. In a constantly changing environment, animals have evolved attention-like processes to effectively filter the incoming sensory stream. These attention-like processes, in turn, are modulated by memory. The neurobiological nature of how attention, action selection and memory are inter-connected is unknown. We describe here new phenotypes of the memory mutant radish in the fruit fly Drosophila.

On the biomarkers and mechanisms of konzo, a distinct upper motor neuron disease associated with food (cassava) cyanogenic exposure.

5 hours ago

Konzo is a self-limiting central motor-system disease associated with food dependency on cassava and low dietary intake of sulfur amino acids (SAA). Under conditions of SAA-deficiency, ingested cassava cyanogens yield metabolites that include thiocyanate and cyanate, a...

The Role of Important Non-Parental Adults (VIPs) in the Lives of Older Adolescents: A Comparison of Three Ethnic Groups.

7 hours ago

Previous research has consistently documented the importance of VIPs (mentors or important non-parental adults) in the lives of adolescents. Little is known, however, about whether VIPs play the same important roles across ethnic groups and whether VIPs remain influential when...

Emerging clinical applications in cardiovascular pharmacogenomics.

15 hours ago

Over one-fourth of the 36 million annual outpatient prescriptions filled in the United States are known to have human genomic biomarker information available that predicts drug safety and efficacy, or both. However, to date, we have not systematically implemented strategies to...

Prepubertal ethanol exposure alters hypothalamic transforming growth factor-α and erbB1 receptor signaling in the female rat.

17 hours ago

Glial-derived transforming growth factor alpha (TGFα) activates the erbB1/erbB2 receptor complex on adjacent glial cells in the medial basal hypothalamus (MBH). This receptor activation stimulates the synthesis and release of prostaglandin-E(2) (PGE(2)) from the glial cells,...

Prokariotic Cell Collection in Denmark

Nov 6 2009

I would like to know about a prokariotic cell collection in Denmark. Is there a cell bank in this country? I need a Lactobacillus strain for a fermentation assay and this information about the bank is very helpful for me.

Request for Entries

Oct 16 2009

Ask the Experts is your chance to get the answers to questions on applications, materials, methods, processes, and technologies. Email you question to bst_web@advantagemedia.com, and the editors of Bioscience Technology will find an appropriate expert to answer it. Watch this space in the future to see the questions your colleagues are posting.

STAY INFORMED: SUBSCRIBE TO

Magazine and E-mail Newsletters

Loading...
E-mail:   

MULTIMEDIA

Video:

Viewing SureFocus Slides

Jun 11 2010

A demonstration of SureFocus Microscope Slides in the review of AFB Smears. SureFocus Slides are a patent-pending breakthrough in tuberculosis detection, as their fluorescent staining circle remains visible during review, Fluorescence Microscopy.

Podcasts:

Allen Institute for Brain Research

Allen Institute for Brain Research

Oct 14 2009

Discussed in this interview are both the mouse brain project and the human cortex project with an emphasis on the importance of these projects to neuroscience research.

Information: