Elevated plasma levels of crosslinked fibrinogen gamma-chain dimer indicate cancer-related fibrin deposition and fibrinolysis.
Cancer-related fibrin deposition and fibrinolysis were investigated by two-dimensional gel electrophoresis of human solid tumor and effusion specimen in addition to plasma samples. Fibrinogen gamma-chain dimer indicating fibrin deposition and plasmin-generated fibrinogen beta-chain fragments were identified in various solid tumor types by amino acid sequencing, mass spectrometry analysis and Western blotting. In tumor-associated effusions, these techniques allowed to observe plasmin-generated fragments of fibrinogen alpha, beta and gamma-chains in addition to elevated levels of acute-phase proteins. Similar observations were made in case of inflammation-associated effusions. No fibrin degradation product was observed in plasma samples, however, high amounts of fibrinogen gamma-chain dimer crosslinked by transglutaminase were detected in plasma from tumor patients, but not in plasma from controls and patients suffering acute infections and/or inflammations. This finding demonstrated that high transglutaminase activity may be associated with cancer. The presented data indicate that the amount of crosslinked fibrinogen gamma-chain dimer in plasma may correlate with tumor-associated fibrin deposition. The tumor-biological relevance of this potential marker protein is discussed.
Gerner
C
C
Institute of Cancer Research, University of Vienna, Austria. Christopher.Gerner@univie.ac.at
Steinkellner
W
W
Holzmann
K
K
Gsur
A
A
Grimm
R
R
Ensinger
C
C
Obrist
P
P
Sauermann
G
G
D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism*; D016022:Case-Control Studies; D003432:Cross-Linking Reagents / Q000378:metabolism*; D019281:Dimerization; D015180:Electrophoresis, Gel, Two-Dimensional; D005337:Fibrin / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism*; D005342:Fibrinolysis; D006487:Hemostasis; D006801:Humans; D009363:Neoplasm Proteins / Q000097:blood / Q000378:metabolism; D009369:Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000378:metabolism; D016066:Pleural Effusion, Malignant / Q000378:metabolism; D020543:Proteome / Q000032:analysis; D014018:Tissue Distribution
D014408:Biomarkers, Tumor; D003432:Cross-Linking Reagents; D009363:Neoplasm Proteins; D020543:Proteome; D005337:Fibrin; D005340:Fibrinogen