Elevated plasma levels of crosslinked fibrinogen gamma-chain dimer indicate cancer-related fibrin deposition and fibrinolysis

Thromb Haemost. 2001 Mar;85(3):494-501.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / metabolism*
  • Case-Control Studies
  • Cross-Linking Reagents / metabolism*
  • Dimerization
  • Electrophoresis, Gel, Two-Dimensional
  • Fibrin / metabolism
  • Fibrinogen / metabolism*
  • Fibrinolysis
  • Hemostasis
  • Humans
  • Neoplasm Proteins / blood
  • Neoplasm Proteins / metabolism
  • Neoplasms / blood
  • Neoplasms / diagnosis*
  • Neoplasms / metabolism
  • Pleural Effusion, Malignant / metabolism
  • Proteome / analysis
  • Tissue Distribution

Substances

  • Biomarkers, Tumor
  • Cross-Linking Reagents
  • Neoplasm Proteins
  • Proteome
  • Fibrin
  • Fibrinogen