Serum amyloid A enhances plasminogen activation: implication for a role in colon cancer.
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.
Michaeli
Amit
A
Hematology Unit, Hadassah-Hebrew University Medical Center, Mount Scopus, 91240 Jerusalem, Israel.
Finci-Yeheskel
Zvezdana
Z
Dishon
Shira
S
Linke
Reinhold P
RP
Levin
Mark
M
Urieli-Shoval
Simcha
S
D003110:Colonic Neoplasms / Q000378:metabolism*; D005341:Fibrinolysin / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D010958:Plasminogen / Q000378:metabolism*; D010960:Plasminogen Activators / Q000378:metabolism*; D000685:Serum Amyloid A Protein / Q000378:metabolism*
D000685:Serum Amyloid A Protein; D010958:Plasminogen; D010960:Plasminogen Activators; D005341:Fibrinolysin