Obesity potentiates the growth and dissemination of pancreatic cancer.
BACKGROUND
Obesity is an independent risk factor for pancreatic cancer development and progression, although the mechanisms underlying this association are completely unknown. The aim of the current study was to investigate the influence of obesity on pancreatic cancer growth using a novel in vivo model.


METHODS
Lean (C57BL/6 J) and obese (Lep(Db) and Lep(Ob)) mice were inoculated with murine pancreatic cancer cells (PAN02), and studied after 5 weeks of tumor growth. Tumor histology was evaluated by hematoxylin and eosin staining, cellular proliferation was assessed by 5-bromodeoxyuridine, and apoptosis was measured by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay. Serum adiponectin, leptin, and insulin levels were assayed.


RESULTS
Obese mice developed larger tumors, and a significantly greater number of mice developed metastases; mortality was also greater in obese mice. Tumor apoptosis did not differ among strains, but tumors from both obese strains had greater proliferation relative to those growing in lean animals. Serum adiponectin concentration correlated negatively and serum insulin concentration correlated positively with tumor proliferation. Intratumoral adipocyte mass in tumors from both obese strains was significantly greater than that in tumors of lean mice.


CONCLUSIONS
Data from this novel in vivo model suggest that the altered adipokine milieu and insulin resistance observed in obesity may lead directly to changes in tumor microenvironment, thereby promoting pancreatic cancer growth and dissemination.
Zyromski
Nicholas J
NJ
Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA. nzyromsk@iupui.edu
Mathur
Abhishek
A
Pitt
Henry A
HA
Wade
Terrence E
TE
Wang
Sue
S
Nakshatri
Poornima
P
Swartz-Basile
Deborah A
DA
Nakshatri
Harikrishna
H
D017667:Adipocytes / Q000473:pathology; D052242:Adiponectin / Q000097:blood; D000818:Animals; D017209:Apoptosis; D001786:Blood Glucose / Q000032:analysis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009765:Obesity / Q000097:blood / Q000150:complications*; D010190:Pancreatic Neoplasms / Q000097:blood / Q000150:complications / Q000473:pathology*
D052242:Adiponectin; D001786:Blood Glucose; D020738:Leptin