Fibrin(ogen) supports tumor cell survival in the lungs by a mechanism coupled to NK cell function. (A-B) Quantitative analysis of metastatic foci within the lungs of mice with single and combined genetic deficits in fibrinogen and NK cells 14 days after intravenous injection of LLC^GFP cells. Note that with natural killer cell function intact (A), Fib^–/– mice developed significantly fewer metastatic foci than control animals challenged in parallel with 4 × 10⁵ LLC^GFP (*P < .01). In contrast, in transgenic mice with a life-long genetic deficit in NK cells (B), fibrinogen deficiency did not significantly alter metastatic potential (8 × 10⁴ cells injected/mouse; P > .5). (C-D) Quantitative analysis of residual radiolabeled LLC^GFP cells within the lung tissue 24 hours after intravenous injection of 8 × 10⁴ cells into mice with and without NK cells. Note that in mice with intact natural killer function (NK⁺), fibrinogen deficiency (n = 15) resulted in a significant diminution in lung-associated tumor cells relative to control animals (n = 18; C). (*P < .008). However, in transgenic mice with a life-long genetic deficit in NK cells (D), no significant diminution in lung-associated tumor cells was observed in Fib^–/– mice (n = 12) relative to control animals (n = 19). All P values were generated using a Mann-Whitney U test.