TY - JOUR
T1 - Obesity potentiates the growth and dissemination of pancreatic cancer
AU - Zyromski, Nicholas J.
AU - Mathur, Abhishek
AU - Pitt, Henry A.
AU - Wade, Terrence E.
AU - Wang, Sue
AU - Nakshatri, Poornima
AU - Swartz-Basile, Deborah A.
AU - Nakshatri, Harikrishna
N1 - Funding Information:
Supported in part by the Society for Surgery of the Alimentary Tract Career Development Award (to N.J.Z.).
Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2009/8
Y1 - 2009/8
N2 - 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 (LepDb and LepOb) 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. Conclusion: 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.
AB - 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 (LepDb and LepOb) 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. Conclusion: 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.
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U2 - 10.1016/j.surg.2009.02.024
DO - 10.1016/j.surg.2009.02.024
M3 - Article
C2 - 19628082
AN - SCOPUS:67650561470
SN - 0039-6060
VL - 146
SP - 258
EP - 263
JO - Surgery
JF - Surgery
IS - 2
ER -