Hemostatic factors support metastasis through both an NK cell-dependent mechanism and at least one additional NK cell-independent mechanism. (A) Quantitative analyses of surface pulmonary foci formed 21 days after intravenous injection of 2 × 10⁵ TF^WT cells into mice with single and combined genetic deficits in fibrinogen (Fib⁻) and natural killer cells (NK⁻). Note that fibrinogen is a significant determinant of metastatic potential in mice with NK cell function, but not in mice lacking NK function. (B) Pulmonary foci in mice with and without NK cells challenged with either TF^WT or TF^O tumor cells. Note that tumor cell–associated TF remains a significant determinant of metastatic potential even in mice lacking NK cell function. (C) Quantitative analysis of [¹²⁵I] -radiolabeled TF^WT (black bars) or TF^O (white bars) tumor cells in the lungs of control (n = 8 for TF^WT and TF^O), fII^Low (n = 4), and Fib⁻ mice (n = 7) 30 minutes after injection of 1 × 10⁵ cells. Note that the majority of tumor cells injected become localized to the lung soon after injection regardless of the presence or absence of tumor cell–associated TF or circulating prothrombin and fibrinogen. (D) Residual [¹²⁵I] -radiolabeled TF^WT cells present in the lungs of mice with single and combined genetic deficits in NK cells and fibrinogen 24 hours after initial tumor cell injection. Note that fibrinogen is a significant determinant of early TF^WT cell survival in the lungs of mice with NK cells (Fib⁺, n = 9; Fib⁻, n = 6), but fibrinogen is not a determinant of early tumor cell survival in mice with a genetic defect in NK cell function (Fib⁺, n = 11; Fib⁻, n = 7). (E) Comparative analysis of the early survival (24 hours after inoculation) of [¹²⁵I] -radiolabeled TF^WT (black bars) and TF^O cells (white bars) in the lungs of mice with NK cells (TF^WT, n = 9; TF^O, n = 6) and without NK cells (TF^WT, n = 11; TF^O, n = 6). Note that TF was an important determinant of residual tumor cell survival in the lungs of mice with and without NK cell function. All P values were generated with the Mann Whitney U test. The horizontal bars in (A) and (B) indicate median values. The error bars in (C) through (E) indicate SEM.