Obesity potentiates the growth and dissemination of pancreatic cancer

Nicholas Zyromski, Abhishek Mathur, Henry A. Pitt, Terrence E. Wade, Sue Wang, Poornima Nakshatri, Deborah A. Swartz-Basile, Harikrishna Nakshatri

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)258-263
Number of pages6
JournalSurgery
Volume146
Issue number2
DOIs
StatePublished - Aug 2009

Fingerprint

Pancreatic Neoplasms
Obesity
Growth
Neoplasms
Obese Mice
Adiponectin
Serum
Insulin
Apoptosis
Adipokines
Tumor Microenvironment
DNA Nucleotidylexotransferase
Bromodeoxyuridine
Hematoxylin
Eosine Yellowish-(YS)
Leptin
Adipocytes
Insulin Resistance
Histology
Cell Proliferation

ASJC Scopus subject areas

  • Surgery

Cite this

Obesity potentiates the growth and dissemination of pancreatic cancer. / Zyromski, Nicholas; Mathur, Abhishek; Pitt, Henry A.; Wade, Terrence E.; Wang, Sue; Nakshatri, Poornima; Swartz-Basile, Deborah A.; Nakshatri, Harikrishna.

In: Surgery, Vol. 146, No. 2, 08.2009, p. 258-263.

Research output: Contribution to journalArticle

Zyromski, N, Mathur, A, Pitt, HA, Wade, TE, Wang, S, Nakshatri, P, Swartz-Basile, DA & Nakshatri, H 2009, 'Obesity potentiates the growth and dissemination of pancreatic cancer', Surgery, vol. 146, no. 2, pp. 258-263. https://doi.org/10.1016/j.surg.2009.02.024
Zyromski N, Mathur A, Pitt HA, Wade TE, Wang S, Nakshatri P et al. Obesity potentiates the growth and dissemination of pancreatic cancer. Surgery. 2009 Aug;146(2):258-263. https://doi.org/10.1016/j.surg.2009.02.024
Zyromski, Nicholas ; Mathur, Abhishek ; Pitt, Henry A. ; Wade, Terrence E. ; Wang, Sue ; Nakshatri, Poornima ; Swartz-Basile, Deborah A. ; Nakshatri, Harikrishna. / Obesity potentiates the growth and dissemination of pancreatic cancer. In: Surgery. 2009 ; Vol. 146, No. 2. pp. 258-263.
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