Insulin, leptin, and tumoral adipocytes promote murine pancreatic cancer growth

J Gastrointest Surg. 2010 Dec;14(12):1888-93; discussion 1893-4. doi: 10.1007/s11605-010-1349-x. Epub 2010 Sep 22.

Abstract

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, 2.5 × 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.

Results: 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.

Conclusion: These data show that diet-induced obesity accelerates the growth of murine pancreatic cancer.

MeSH terms

  • Adipocytes / physiology*
  • Animals
  • Cell Proliferation
  • Female
  • Insulin / physiology*
  • Leptin / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Obesity / complications*
  • Pancreatic Neoplasms / etiology*
  • Pancreatic Neoplasms / pathology*

Substances

  • Insulin
  • Leptin