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Blood-clotting protein linked to cancer and septicemia
Date:2/4/2011

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 r
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Contact: Sonia Furtado
sonia.furtado@embl.de
European Molecular Biology Laboratory
Source:Eurekalert

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