Insulin, Leptin, and Tumoral Adipocytes Promote Murine Pancreatic Cancer Growth

Department of Surgery, Indiana University School of Medicine, 535 Barnhill Dr. RT 130, Indianapolis, IN 46202, USA.
Journal of Gastrointestinal Surgery (Impact Factor: 2.8). 12/2010; 14(12):1888-93; discussion 1893-4. DOI: 10.1007/s11605-010-1349-x
Source: PubMed


Obesity accelerates development and growth of human pancreatic cancer. We recently reported similar findings in a novel murine model of pancreatic cancer in congenitally obese mice. The current experiments were designed to evaluate the effects of diet-induced obesity on pancreatic cancer growth.
Thirty C57BL/6J female mice were fed either control 10% fat (n = 10) or 60% fat diet (n = 20) starting at age 6 weeks. At 11 weeks, 2.5 × 10(5) PAN02 murine pancreatic cancer cells were inoculated. After 6 weeks, tumors were harvested. Serum adiponectin, leptin, insulin, and glucose concentrations were measured. Tumor proliferation, apoptosis, adipocyte content, and tumor-infiltrating lymphocytes were evaluated.
The diet-induced obesity diet led to significant weight gain (control 21.3 ± 0.6 g; diet-induced obesity 23.1 ± 0.5 g; p = 0.03). Mice heavier than 23.1 g were considered "Overweight." Tumors grew significantly larger in overweight (1.3 ± 0.3 g) compared to lean (0.5 ± 0.2 g; p = 0.03) mice; tumor size correlated positively with body weight (R = 0.56; p < 0.02). Serum leptin (3.1 ± 0.7 vs. 1.4 ± 0.2 ng/ml) and insulin (0.5 ± 0.2 vs. 0.18 ± 0.02 ng/ml) were significantly greater in overweight mice. Tumor proliferation, apoptosis, and tumor adipocyte volume were similar. T and B lymphocytes were observed infiltrating tumors from lean and overweight mice in similar number.
These data show that diet-induced obesity accelerates the growth of murine pancreatic cancer.

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    • "Insulin levels correlated positively with body weight and tumour proliferation and inversely with tumour cell apoptosis in this study. Larger tumours were also found in an obese, hyperinsulinaemic mouse model of pancreatic cancer compared to lean counterparts [24]. In these rodent models, differentiation of high insulin levels-induced effects from increased body weight and fat mass effects is not always possible. "
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