Experimental metastasis and primary tumor growth in mice with hemophilia A

• Published in: Journal of thrombosis and haemostasis 2006-05, Vol.4 (5), p.1056-1062
• Main Authors: LANGER, F., AMIRKHOSRAVI, A., INGERSOLL, S. B., WALKER, J. M., SPATH, B., EIFRIG, B., BOKEMEYER, C., FRANCIS, J. L.
• Format: Article
• Language: English
• Subjects: Animals; B16F10 melanoma; Cell Division; Cell Line, Tumor; coagulation; Flow Cytometry; hemophilia A; Hemophilia A - pathology; Male; metastasis; Mice; Neoplasm Metastasis; Reverse Transcriptase Polymerase Chain Reaction; tissue factor
• ISSN: 1538-7933; 1538-7836; 1538-7836
• DOI: 10.1111/j.1538-7836.2006.01883.x

During experimental lung metastasis, tumor cells adhere to the pulmonary microvasculature and activate coagulation via surface‐expressed tissue factor (TF), leading to local fibrin deposition and platelet aggregation. While interventional studies have demonstrated great efficacy of anticoagulants and antiplatelet agents in inhibiting metastasis, no information is available on how tumor biology may be affected by congenital bleeding disorders such as hemophilia A. We therefore used a syngeneic model to study experimental metastasis and primary tumor growth in factor VIII (FVIII)‐deficient mice. By conventional reverse transcription‐polymerase chain reaction, flow cytometry, and one‐stage clotting assays, we demonstrated constitutive expression of TF mRNA, antigen, and procoagulant activity in the murine B16F10 melanoma cell line. In hemophilic mice, B16F10 lung metastasis was significantly (P