Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Blood-clotting protein linked to cancer and septicaemia

04.02.2011
Research could lead to new therapies

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.

Policy regarding use
EMBL press and picture releases including photographs, graphics, movies and videos are copyrighted by EMBL. They may be freely reprinted and distributed for non-commercial use via print, broadcast and electronic media, provided that proper attribution to authors, photographers and designers is made.
Sonia Furtado
EMBL Press Officer
Meyerhofstr. 1, 69117 Heidelberg, Germany
Tel.: +49 (0)6221 387 8263
Fax: +49 (0)6221 387 8525
sonia.furtado@embl.de

Sonia Furtado | EMBL Research News
Further information:
http://www.embl.org

More articles from Life Sciences:

nachricht CRISPR meets single-cell sequencing in new screening method
19.01.2017 | CeMM Forschungszentrum für Molekulare Medizin der Österreichischen Akademie der Wissenschaften

nachricht Toward a 'smart' patch that automatically delivers insulin when needed
18.01.2017 | American Chemical Society

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

The Great Unknown: Risk-Taking Behavior in Adolescents

19.01.2017 | Studies and Analyses

Magnetic moment of a single antiproton determined with greatest precision ever

19.01.2017 | Physics and Astronomy

CRISPR meets single-cell sequencing in new screening method

19.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>