Figure 3. Targeted deletion of PPARγin macrophages inhibits lung cancer metastasis in an orthotopic mouse model of non-small cell lung cancer.

Following lethal irradiation, WT C57BL/6 mice received bone marrow from either PPARγ-Mac^neg (KO) or PPARγ^flox/flox (Flox) donor mice as described in the “Methods” section. After 5 weeks recovery to allow engraftment, mice were placed on either pioglitazone-containing chow or control chow for 1 week prior to tumor cell implantation and throughout the course of the experiment. Animals were injected with 10⁵ CMT/167-luc cells orthotopically as in Fig. 1. Four weeks after cancer cell inoculation, animals were imaged by bioluminescence and sacrificed. A. The number of secondary lung tumors was quantitated by examination under a dissecting microscope. Tumors were counted by two independent blinded observers. Data are means and s.e.m. of counts from 6–9 animals in each group. Mice receiving PPARγ-Mac^neg bone marrow had significantly fewer numbers of secondary lung tumors than mice receiving PPARγ^flox/flox. *P<0.05 vs Flox control. **P<0.05 vs Flox control. B. Representative histology (H&E) is shown for secondary lung tumors from all 4 groups of animals. C. Tumor-bearing lung sections from WT PPARγ^flox/flox or PPARγ-Mac^neg mice were immunohistochemically stained for arginase I (brown reaction color). Representative images are shown of lungs from all 4 groups of animals. D. The number of arginase I-positive cells was quantitated by two independent blinded observers. Data are means and s.e.m. of counts from 6–9 animals in each group. Lungs from PPARγ-Mac^neg mice on control chow showed a statistical decrease in arginase I positive cells; pioglitazone increased the number of these cells to levels seen in PPARγ^flox/flox mice. *P<0.05 vs Flox control.