TM influences metastasis primarily via regulation of thrombin function. (A) Quantification of pulmonary foci in WT and TMPro mice 21 days after IV injection of 3 × 105 TF-expressing fibrosarcoma cells (●) or 1 × 106 TF-deficient fibrosarcoma cells (♢). Note that TF-deficient cells were rarely successful in forming metastases, regardless of mouse genotype, even at doses significantly greater than those used to evaluate TF-expressing cells. (B) Diminution of prothrombin levels with a prothrombin specific ASO significantly diminished the number of pulmonary metastases formed 10 days after IV injection of 3 × 105 LLCGFP cells in both WT and TMPro mice. (C) Similarly, reduction of circulating platelets with a platelet-specific antibody resulted in a near complete abrogation of pulmonary metastases formed after IV injection of LLCGFP cells in both WT and TMPro mice. (D) TMLeD mice developed a similar number of pulmonary metastases compared with WT mice after intravenous injection of 3.5 × 104 B16 melanoma cells.
