Figure 5.

CCR2 KO mice and HNF4α rescue the early changes in liver metabolism in pancreatic cancer–bearing mice. A, Hematoxylin and eosin staining demonstrates decreased immune cell infiltration to the livers of CCR2^−/− pancreatic cancer–bearing mice compared with livers of pancreatic cancer–bearing WT mice. Pancreatic cancer–bearing mice were mice injected with KPC. Magnifications: 10, 20, and 40× as detailed in the figure. B, ELISA demonstrates decreased IL6 levels in the plasma of pancreatic cancer CCR2^−/−–bearing mice relative to pancreatic cancer–bearing WT mice (PC WT n = 7, CCR2^−/−n = 6, Student t test). P = 0.0125. C, RT-PCR of livers from CCR2^−/− pancreatic cancer–bearing mice demonstrates preserved RNA expression levels of Ass1, Otc, Alb, and Hnf4a compared with decreased expression levels of these genes in livers of pancreatic cancer–bearing WT mice (PC WT n = 5, CCR2^−/−n = 6, Student t test). P = 0.019, 0.011, 0.002, respectively. D, Decreased levels of aspartate and glutamate in the liver of pancreatic cancer CCR2^−/−–bearing mice. UC intermediate levels were measured with gas chromatography–mass spectrometry (n = 7, Student t test). P = 0.011, 0.029, respectively. E, Weight measurements and nuclear magnetic resonance (NMR) body composition analysis of CCR2^−/− pancreatic cancer–bearing mice demonstrate significantly less weight loss (left), increased fat tissue (middle), and decreased free fluids (right) in comparison with WT pancreatic cancer on day 21 (relative to day 0; n = 7 in each group, Student t test). P = 0.014, 0.006, and 0.004, respectively. F, Tumor weights measured on the day of sacrifice are significantly lower in the CCR2^−/− mice with pancreatic cancer compared with WT pancreatic cancer (n = 7, Student t test). P = 0.009. G, Pancreatic cancer tumor growth is significantly more prominent in mice injected with AAV-GFP compared with AAV-HNF4α (AAV-GFP n = 4, AAV-HNF4α n = 9, Student t test). P = 0.006. H, Mice with pancreatic cancer injected with AAV-HNF4α demonstrate a significant increase in survival compared with those injected with AAV-GFP [log-rank (Mantel–Cox) test]. P = 0.02. I, Mice with pancreatic cancer injected with AAV-HNF4α maintain weight compared with those injected with AAV-GFP (AAV-GFP n = 8, AAV-HNF4α n = 9, two-way ANOVA). P = 0.05. J, NMR body composition analysis of mice with pancreatic cancer injected with AAV-HNF4α demonstrate less fat tissue loss (left) and decreased free fluid accumulation (right) in comparison with mice with pancreatic cancer injected with AAV-GFP (AAV-GFP n = 5, AAV-HNF4α n = 6, Student t test). P = 0.007, 0.012, respectively.