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, 2.5 × 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.


CONCLUSIONS
These data show that diet-induced obesity accelerates the growth of murine pancreatic cancer.
White
Patrick B
PB
Department of Surgery, Indiana University School of Medicine, 535 Barnhill Dr. RT 130, Indianapolis, IN 46202, USA. pbwhite@iupui.edu
True
Eben M
EM
Ziegler
Kathryn M
KM
Wang
Sue S
SS
Swartz-Basile
Deborah A
DA
Pitt
Henry A
HA
Zyromski
Nicholas J
NJ
D017667:Adipocytes / Q000502:physiology*; D000818:Animals; D049109:Cell Proliferation; D005260:Female; D007328:Insulin / Q000502:physiology*; D020738:Leptin / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications*; D010190:Pancreatic Neoplasms / Q000209:etiology* / Q000473:pathology*
D007328:Insulin; D020738:Leptin