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New clues to how cancer-related proteins plasmin, thrombin lose inhibition
Date:10/19/2010

RICHLAND, Wash. -- A new technique that searches blood for the tiniest remnants of broken down proteins has revealed new information about how cells crank up cancer activators called proteases. The results improve researchers' understanding of the mechanics of breast cancer and point to where to look for possible indicators of early disease.

Appearing this week in PLoS ONE, the research shows previously unknown contributing factors to protease activation, which helps spread cancer: cancer cells almost completely chew up small protein pieces that normally put the brakes on two proteases known as plasmin and thrombin. The loss of these brakes -- known as protease inhibitors antiplasmin and antithrombin -- occur considerably more in blood from cancer patients compared to healthy persons' blood.

Although researchers have long known that proteases become activated by cancer, this work led by researchers at the Department of Energy's Pacific Northwest National Laboratory shows two new possible mechanisms how. This work was supported by the NIH National Center for Research Resources.

Future work that measures how these proteins function in early and late stage cancer patients might reveal useful biomarkers for diagnosis.

Losing it

Cancer is largely about losing control of a cell's tightly regulated life cycle. Growing unrestrained, cancers consume bodily resources such as energy and tissue. One protein that loses control in breast and other cancers, plasmin, encourages the breakdown of the tissue matrix that keeps cells strapped together. This allows cancer cells to spread to other parts of the body. However, researchers have yet to fully work out the molecular chain of events inside and outside cells that leads to overactive plasmin.

In this work, scientists examined cellular shrapnel for clues. As cancer retunes cells to its own nefarious ends, proteins normally in use get chopped up. The cast-off
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Contact: Mary Beckman
mary.beckman@pnl.gov
509-375-3688
DOE/Pacific Northwest National Laboratory
Source:Eurekalert

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