Figure 5. (See also Figure S5): Prolonged reduction of AngII production restrains the tumor-promoting TAM response and delays tumor mortality in KP mice.

A. Quantification of splenic and bone marrow-derived HSCs and MDPs in four cohorts of mice. From left to right: age-matched control mice (−cancer, n=13); tumor-bearing KP mice (+cancer, n=13), KP mice treated with enalapril (+Cancer +enalapril; n=8) and KP mice treated with hydralazine (+cancer +hydralazine; n=3). Tumor-bearing mice were analyzed at 11 wk post tumor initiation. Administration of enalapril or hydralazine started at wk 8.

B. Quantification of splenic monocytes (top) and lung macrophages (bottom) in the same mice as in A.

C. Phenotypic characterization of lung macrophages. F4/80⁺ CD11c^int/+ Lin⁻ macrophages (Lin defined as [B220/CD19/CD90.2/DX5/NK1.1/Ly-6G]^lo) were isolated from lungs of control mice (−cancer), tumor-bearing KP mice (+cancer) and tumor-bearing KP mice treated with enalapril (+cancer +enalapril). Mice were analyzed at 11 wk post tumor initiation. Treatment with enalapril started at wk 8. Data show relative mRNA expression levels (real time PCR) normalized to 18s rRNA. Analysis of Actb (Actin-b) expression was included as an internal control.

D. Number (top) and total volume (bottom) of lung tumors detected by high resolution CT at 11 wk post tumor initiation in KP mice. The legend identifies mice that started a treatment with enalapril or hydralazine at wk 8.

E. Representative 3D volume renderings of tumors at week 11 (Wk 11) from mice treated (bottom) or not (top) with enalapril for 3 consecutive weeks. Tumors are shown in red, lungs in green and bones in yellow.

F. Kaplan-Meier survival analysis of KP mice treated (n=12) or not (n=14) with enalapril starting at wk 8 post tumor initiation.

Data in A–B and D are presented as median with dots indicating measurements for single mice. Data in C are presented as mean ± SEM. *, p<0.05; **, p<0.01, ***, p<0.001; ns, non-significant.