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Serum amyloid A enhances plasminogen activation: implication for a role in colon cancer.

Michaeli A, Finci-Yeheskel Z, Dishon S, Linke RP, Levin M, Urieli-Shoval S

Hematology Unit, Hadassah-Hebrew University Medical Center, Mount Scopus, 91240 Jerusalem, Israel.

We have recently reported that the acute phase protein serum amyloid A (SAA), is locally and differentially expressed in neoplastic tissues of human colon. In the present study, we demonstrate that SAA enhances the plasminogen activation (PA)-activity of HT-29 colon cancer cell line. Cell-associated PA-activity was measured following the plasminogen-dependent ability of the cells to cleave the chromogenic substrate S-2251. The SAA-enhanced PA-activity was inhibited by anti-SAA antibodies. These antibodies also decreased the basal PA-activity of HT-29 cells and neutralized their cytokines (Interleukin-1beta+Interleukin-6)-enhanced PA-activity. Using specific chromogenic substrates and the fibrin clot-lysis assay, we found that SAA enhances also the PA-activity mediated by purified urokinase- and tissue-type plasminogen activators. Together, the data indicate that SAA enhances plasminogen activation and suggest its possible role in plasmin(ogen)-mediated colon cancer progression.

Published 25 February 2008 in Biochem Biophys Res Commun, 368(2): 368-73.
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