title: Colon cancer metastasis in mouse liver is not affected by hypercoagulability due to Factor V Leiden mutation.
abstract: Clinical trials have shown life-prolonging effects of antithrombotics in cancer patients, but the molecular mechanisms remain unknown due to the multitude of their effects. We investigated in a mouse model whether one of the targets of antithrombotic therapy, fibrin deposition, stimulates tumour development. Fibrin may provide either protection of cancer cells in the circulation against mechanical stress and the immune system, or form a matrix for tumours and/or angiogenesis in tumours to develop. Mice homozygous for Factor V Leiden (FVL), a mutation in one of the coagulation factors that facilitates fibrin formation, were used to investigate whether hypercoagulability affects tumour development in an experimental metastasis model. Liver metastases of colon cancer were induced in mice with the FVL mutation and wild-type littermates. At day 21, number and size of tumours at the liver surface, fibrin/fibrinogen distribution, vessel density and the presence of newly formed vessels in tumours were analysed. Number and size of tumours did not differ between mice with and without the FVL mutation. Fibrin/fibrinogen was found in the cytoplasm of hepatocytes and cancer cells, in blood vessels in liver and tumour tissue and diffusely distributed outside vessels in tumours, indicating leaky vessels. Vessel density and angiogenesis varied widely between tumours, but a pre-dominance for vessel-rich or vessel-poor tumours or vessel formation could not be found in either genotype. In conclusion, the FVL mutation has no effect on the development of secondary tumours of colon cancer in livers of mice. Fibrin deposition and thus inhibition of fibrin formation by anticoagulants do not seem to affect tumour development in this model.
authors.affiliation: Academic Medical Center, Department of Cell Biology and Histology, University of Amsterdam, The Netherlands.
authors.forename: C P W
authors.initials: CP
authors.lastname: Klerk
authors.forename: S M
authors.initials: SM
authors.lastname: Smorenburg
authors.forename: C A
authors.initials: CA
authors.lastname: Spek
authors.forename: C J F
authors.initials: CJ
authors.lastname: Van Noorden
mesh_terms: D000818:Animals; D003110:Colonic Neoplasms / Q000098:blood supply / Q000473:pathology*; D003593:Cytoplasm / Q000473:pathology; D042783:Endothelial Cells / Q000473:pathology; D005165:Factor V / Q000235:genetics*; D005337:Fibrin / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D006720:Homozygote; D008113:Liver Neoplasms / Q000098:blood supply / Q000473:pathology / Q000556:secondary*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics*; D009362:Neoplasm Metastasis; D021381:Protein Transport; D019851:Thrombophilia / Q000150:complications*; D047368:Tumor Burden
chemical_list: C095381:factor V Leiden; D005165:Factor V; D005337:Fibrin; D005340:Fibrinogen