Elevated Plasma Levels of Crosslinked Fibrinogen Gamma-chain Dimer Indicate Cancer-related Fibrin Deposition and Fibrinolysis

Christopher Gerner; Werner Steinkellner; Klaus Holzmann; Andrea Gsur; Rudolf Grimm; Christian Ensinger; Peter Obrist; Georg Sauermann

doi:10.1055/s-0037-1615611

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2001; 85(03): 494-501
DOI: 10.1055/s-0037-1615611

Review Article

Schattauer GmbH

Elevated Plasma Levels of Crosslinked Fibrinogen Gamma-chain Dimer Indicate Cancer-related Fibrin Deposition and Fibrinolysis

Christopher Gerner

¹Institute of Cancer Research, University of Vienna, Vienna, Austria

,

Werner Steinkellner

²Otto-Warburg Society for Research in Immunology and Oncology, Grünburg, Austria

,

Klaus Holzmann

¹Institute of Cancer Research, University of Vienna, Vienna, Austria

,

Andrea Gsur

¹Institute of Cancer Research, University of Vienna, Vienna, Austria

,

Rudolf Grimm

³Hewlett Packard, Chemical Analytical Division, Waldbronn, Germany

,

Christian Ensinger

⁴Institute of Pathology, University of Innsbruck, Innsbruck, Austria

,

Peter Obrist

⁴Institute of Pathology, University of Innsbruck, Innsbruck, Austria

,

Georg Sauermann

¹Institute of Cancer Research, University of Vienna, Vienna, Austria

› Author Affiliations

Abstract

Summary

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.

Keywords

Cancer - fibrin deposition - fibrinolysis - plasma proteins - two-dimensional gel electrophoresis

Full Text

References

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