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

of protein changes in very specific biological systems."

These biological systems included two proteases and their corresponding inhibitors -- plasmin and antiplasmin, thrombin and antithrombin -- which keep healthy cells growing properly.

When the researchers compared all the different pieces of plasmin found in the cancer samples to the healthy samples, two fragments stood out. The team found one of them, a cut-up Plg preactivation peptide, chopped seven times more often in the cancer sample than in the healthy sample. This would lead to an increase in plasmin activation in the cancer patients.

The other stand-out fragment arose from antiplasmin, and the scientists only found it in blood from cancer patients. Because antiplasmin normally prevents plasmin from destroying the environment around cells, the presence of the cut fragment meant plasmin was free to do damage.

The researchers found a similar situation with thrombin, a protease that helps blood vessels form. The cancer samples harbored fewer intact molecules of its inhibitor, antithrombin, allowing the cancer to build vessels to bring in nourishment.

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Normally, backup systems exist to deal with proteases that have gone wrong. But the scientists found evidence that the backup systems were damaged in the cancer samples as well. The team found fragments from three important backup systems: protein clusters that protect the extracellular matrix around cells; several key elements of the immune system that can scan for and kill cancer cells; and other proteins that normally suppress cells from turning cancerous.

Taken together, all these dysfunctional systems mean cells and their environment are helpless against attack by the activated proteases.

Because the team combined samples from early through late stage cancer patients, additional work is needed to determine whether either of these fragments would show up in blo
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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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