Featured Research

from universities, journals, and other organizations

Blood-clotting protein linked to cancer and septicemia

Date:
February 5, 2011
Source:
European Molecular Biology Laboratory (EMBL)
Summary:
Scientists have discovered how stressed cells boost the production of the key blood-clotting factor, thrombin. Their work shows how cancer cells may be taking advantage of this process, and opens new possibilities for fighting back against cancer and septicemia.

Scientists in a collaboration between EMBL Heidelberg and the University of Heidelberg Medical Centre have discovered how stressed cells boost the production of the key blood-clotting factor, thrombin. Their work shows how cancer cells may be taking advantage of this process, and opens new possibilities for fighting back against cancer and septicemia.

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 February 4 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 septicemia, 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 septicemia therapies."

The Heidelberg scientists found that p38 MAPK also influences thrombin production during septicemia. Also known as blood poisoning, septicemia 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 septicemia 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.


Story Source:

The above story is based on materials provided by European Molecular Biology Laboratory (EMBL). Note: Materials may be edited for content and length.


Journal Reference:

  1. Sven Danckwardt, Anne-Susan Gantzert, Stephan Macher-Goeppinger, Hans Christian Probst, Marc Gentzel, Matthias Wilm, Hermann-Josef Grφne, Peter Schirmacher, Matthias W. Hentze, Andreas E. Kulozik. p38 MAPK Controls Prothrombin Expression by Regulated RNA 3′ End Processing. Molecular Cell, 2011; 41 (3): 298 DOI: 10.1016/j.molcel.2010.12.032

Cite This Page:

European Molecular Biology Laboratory (EMBL). "Blood-clotting protein linked to cancer and septicemia." ScienceDaily. ScienceDaily, 5 February 2011. <www.sciencedaily.com/releases/2011/02/110204091253.htm>.
European Molecular Biology Laboratory (EMBL). (2011, February 5). Blood-clotting protein linked to cancer and septicemia. ScienceDaily. Retrieved April 17, 2014 from www.sciencedaily.com/releases/2011/02/110204091253.htm
European Molecular Biology Laboratory (EMBL). "Blood-clotting protein linked to cancer and septicemia." ScienceDaily. www.sciencedaily.com/releases/2011/02/110204091253.htm (accessed April 17, 2014).

Share This



More Health & Medicine News

Thursday, April 17, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Could Even Casual Marijuana Use Alter Your Brain?

Could Even Casual Marijuana Use Alter Your Brain?

Newsy (Apr. 16, 2014) — A new study conducted by researchers at Northwestern and Harvard suggests even casual marijuana use can alter your brain. Video provided by Newsy
Powered by NewsLook.com
Thousands Of Vials Of SARS Virus Go Missing

Thousands Of Vials Of SARS Virus Go Missing

Newsy (Apr. 16, 2014) — A research institute in Paris somehow misplaced more than 2,000 vials of the deadly SARS virus. Video provided by Newsy
Powered by NewsLook.com
Formerly Conjoined Twins Released From Dallas Hospital

Formerly Conjoined Twins Released From Dallas Hospital

Newsy (Apr. 16, 2014) — Conjoined twins Emmett and Owen Ezell were separated by doctors in August. Now, nearly nine months later, they're being released from the hospital. Video provided by Newsy
Powered by NewsLook.com
Ebola Outbreak Now Linked To 121 Deaths

Ebola Outbreak Now Linked To 121 Deaths

Newsy (Apr. 15, 2014) — The ebola virus outbreak in West Africa is now linked to 121 deaths. Health officials fear the virus will continue to spread in urban areas. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins