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Warfarin inhibits metastasis in the animal model and injection of the Warfarin-dependent coagulation factor complex II, IX, X enhances pulmonary metastasis in the same model. We have studied two possible mechanisms responsible for the observed effect. Mtln3, rat mammary carcinoma cells, radiolabelled with 5-(125) Iodo-2'-deoxyuridine (IUDR) were injected intravenously in female Fisher 344 rats either alone or in combination with factor complex II, IX, X or bovine serum albumin. Following sacrifice at various intervals, measured lung radioactivity was significantly higher (20%) in animals administered cells with the factor complex than in the other two groups (P less than 0.001, ANOVA and Student's t-test). These results indicate increased entrapment of tumour cells in the pulmonary microcirculation. In a second experiment, rat factor complex II, IX, X was prepared, and Mtln3 cells were then injected in female Fisher 344 rats alone or in combination with either human factor complex or rat factor complex. Following sacrifice, the number of pulmonary nodules in animals receiving cells with rat factor complex was similar to that in animals receiving human factor complex, and significantly higher than that in the control (P less than 0.001, ANOVA and Mann-Whitney), indicating that the observed enhancement of pulmonary seeding is unrelated to the xenogeneic properties of the human factor complex.

Original publication

DOI

10.1038/bjc.1991.340

Type

Journal article

Journal

British journal of cancer

Publication Date

09/1991

Volume

64

Pages

513 - 517

Addresses

University Department of Surgery, Western Infirmary, Glasgow, UK.

Keywords

Animals, Rats, Inbred F344, Humans, Rats, Adenocarcinoma, Mammary Neoplasms, Experimental, Lung Neoplasms, Neoplasm Metastasis, Iodine Radioisotopes, 9,10-Dimethyl-1,2-benzanthracene, Prothrombin, Factor IX, Factor X, Idoxuridine, Tumor Stem Cell Assay, Cell Division, Female