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

Background 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 Methods 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 5x10(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 Results The diet-induced obesity diet led to significant weight gain (control 21 3 +/- 06 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 Conclusion These data show that diet-induced obesity accelerates the growth of murine pancreatic cancer