Monoclonal antibodies for immunodetection of fibrin deposits on cancer cells

Abstract

The progression of a tumor from benign to malign and localized to invasive and metastatic growth is the major cause of poor outcome of therapy in cancer patients. The deposition of fibrin along with other procoagulant molecules into the extracellular matrix obviously serves as a scaffold to support proliferation, migration and tumor cell growth as well as protection against the immune system. The use of antibodies as agents for the immunodetection of fibrin deposits in vivo has been hampered by anti-fibrin cross-reactivities with fibrinogen. For the immunohistochemical detection of fibrin we used highly specific monoclonal antibodies to a synthetic fibrinunique peptide, because the fibrin molecule shares many epitopes with fibrinogen. The monoclonal antibody was applied to adenocarcinoma of colon, mamma, pancreas, sarcoma and acute myeloic leukemia. In all tissue sections and cytospin preparations fibrin was identified in a direct apposition to the surface membranes of carcinoma and sarcoma cells, predominantly at the host-tumor interface and also in regions directly adjacent to zones of angiogenesis, whereas normal cells and tissue showed no deposits of fibrin. The findings will be supported by investigations that factors and components of the coagulation system could be detected in the tumor stroma and tumor cells. These factors are obviously produced and secreted by the malignant cells and deposited together with fibrinogen into the extracellular matrix. Our results show that basically all malignant cells examined, independently of ectodermal or mesenchymal derivation, themselves are the origin of hypercoagulability and fibrinolytic system inhibition