Experimental melanoma metastasis in lungs of mice with congenital coagulation disorders.
Experimental animal studies as well as clinical trials have shown that interventions targeting the blood coagulation cascade inhibit cancer cell metastasis. These data support the hypothesis that congenital prothrombotic disorders, like factor V Leiden, facilitate metastasis whereas bleeding disorders, like haemophilia impede metastasis. To test this hypothesis, we subjected factor V Leiden and factor VIII deficient mice to a murine model of experimental lung metastasis. In this model, B16F10 murine melanoma cells are injected into the tail vein resulting in multiple lung metastases within 20 days. Both hemi- and homozygous factor VIII deficient mice were protected against lung metastasis compared to wild-type littermate controls. In contrast, homozygous factor V Leiden mice developed more metastases than wild-type littermates, whereas heterozygous carriers showed an intermediate number of pulmonary foci. Overall, these data show that a congenital susceptibility to either bleeding or thrombosis modifies the metastatic capacity of cancer cells in the bloodstream and suggest that procoagulant phenotypes are a risk factor for tumour metastasis.
Brüggemann
Lois W
LW
Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
Versteeg
Henri H
HH
Niers
Tatjana M
TM
Reitsma
Pieter H
PH
Spek
C Arnold
CA
D000818:Animals; D001778:Blood Coagulation Disorders / Q000151:congenital*; D005165:Factor V / Q000378:metabolism; D005169:Factor VIII / Q000378:metabolism; D005838:Genotype; D008175:Lung Neoplasms / Q000556:secondary*; D008546:Melanoma, Experimental / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D047368:Tumor Burden
C095381:factor V Leiden; D005165:Factor V; D005169:Factor VIII