Figure 10. ET_AR mediates lung metastasis and inflammation.

Female nude mice were injected via tail vein with UMUC3. One cohort of the mice (ZD-pre) received ZD4054 (10 mg/kg/d) 24 hours prior to inoculation, while another received it 1 week after (ZD-post) tail vein injection. Vehicle control (VC) was given to the third cohort before inoculation. (A) The number of animals developing lung metastases 6 weeks after tail vein injection, as well as the number of visible metastases per lung in each cohort. *P < 0.002, χ² test; ^#P < 0.01, Student’s t test. (B) Scatter plot of the incidence and number of visible lung metastases counted 6 weeks after tail vein injection of UMUC3 cells (1 × 10⁶ cells/100 μl) in nude mice with and without treatment with the ET_BR blocker BQ788 before (BQ-pre) or after (BQ-post) UMUC3 injection (500 μM/500 μl PBS/mouse/d). (C) Immunostaining of macrophages infiltrating (×100 magnification) metastatic tumor foci in lungs (tumor) and in the surrounding lung tissue (parenchyma). Bars represent mean ± SEM of the number of macrophages/HPF. *P < 0.05, Student’s t test, as compared with VC-treated mice; ^#P < 0.05, Student’s t test, comparing lungs from ZD-pretreated animals with their ZD-post-treated counterparts. (D) Human and murine IL-6 and MCP-1 were determined in lung lysates 6 weeks after UMUC3 injection in the 3 cohorts described in A. *P < 0.05, Student’s t test, as compared with VC-treated mice; ^#P < 0.05, comparing lungs from ZD-post-treated with their ZD-pretreated counterparts.