NOS2 deficiency delays melanoma progression by inhibiting tumor cell dissemination (A–C) 6-mo follow-up of melanoma development from Ret (n = 40) and RetNos2KO (n = 40) mice. (A,B) Time courses of primary tumor and cutaneous metastasis onset. Mice were examined every 2 weeks. (C) Survival curve. (Mantel-Cox test (A–C)). (D, E) trp2 expression was measured by qRT-PCR in bladders (D) and tumor dLNs (E) collected from Ret and RetNos2KO mice aged of 2, 5 or 12 weeks. Expressions were normalized using GAPDH. Each point represents one mouse. (F) Number of pulmonary metastasis in WT mice and Nos2KO mice after i.v. injections of 105 (n = 8 WT, n = 9 Nos2KO) or 106 (n = 6 per group) B16 melanoma cells. Data are pooled from two independent experiments (mean ± SEM) (Mann–Whitney test). *p < 0.05, **p < 0.01.