Abstract 510: Do adipocytes in the tumor microenvironment influence the growth of pancreatic cancer

Abstract

Abstract Introduction: Pancreatic cancer develops more frequently and progresses more rapidly in obesity. The mechanisms influencing this association are incompletely understood. Using our murine model of pancreatic cancer in diet-induced obesity, we hypothesized that changes in the immune profile and tumor microenvironment may contribute to accelerated pancreatic cancer growth in obesity. Methods: Thirty male C57BL/6J mice were studied. At 5 weeks of age, 20 mice were fed high fat diet (60% fat; HFD) and 10 were fed low fat (10% fat) diet. At 19 weeks of age all mice were inoculated in the flank with 2.5 x105 Pan02 murine pancreatic cancer cells. After 5 weeks of tumor growth, spleens and tumors were collected, splenic flow cytometry evaluated lymphocyte population, proliferation was determined by PCNA staining, and tumor infiltrating lymphocytes (TIL), both B and T, were scored by immunohistochemistry. Intratumoral adipocyte volume was assessed by H&E staining. Students's t-test and Pearson's correlation were applied where appropriate. P value <0.05 was accepted as statistically significant. Results: Mice were segregated into overweight (OW – heavier than the mean body weight of the HFD mice – 35.5g, n=15) and lean (<35.5g, n=14). OW mice were significantly heavier (37.3±0.2g vs. 33.9±0.3g, p<0.001). Tumors were twice as large in OW mice as in lean mice (1.23±0.2g vs. 0.6±0.1g; p=0.001). The peripheral lymphocyte profile was similar in both OW and lean animals (T cells: 51.2±2.5% vs. 49.2±2.3%, p=0.59; B cells: 32.9±1.0% vs. 32.0±1.9%, p=0.73). TIL were observed in similar numbers in both OW and lean groups (T cell: 1.31±0.18 vs. 1.54±0.16, p=0.35; B cell: 0.63±0.08 vs. 0.91±0.15, p=0.33). Tumor proliferation as measured by PCNA was similar in both groups (139±18 OW vs. 143±14 lean, p=0.85). Interestingly, adipocyte volume was significantly greater in the OW tumor microenvironment than in the lean tumors (3.7%±0.7 vs. 2.2%±0.3, p<0.05). Conclusions: These results demonstrate that: 1) tumor weight was significantly greater in OW mice; 2) peripheral and tumor infiltrating lymphocyte profile was similar in OW and lean animals; and 3) adipocyte volume was significantly greater in the tumor microenvironment of OW mice. We conclude that obesity accelerates the growth of pancreatic cancer, and adipocytes in the tumor microenvironment may directly influence tumor growth. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 510. doi:10.1158/1538-7445.AM2011-510