Diet-induced obesity potentiates the growth of gastric cancer in mice

Li,Hai-Jun; Che,Xiang-Ming; Zhao,Wei; He,Shi-Cai; Zhang,Zheng-Liang; Chen,Rui

doi:10.3892/etm.2012.657

Diet-induced obesity potentiates the growth of gastric cancer in mice

Authors:
- Hai-Jun Li
- Xiang-Ming Che
- Wei Zhao
- Shi-Cai He
- Zheng-Liang Zhang
- Rui Chen
View Affiliations

Affiliations: Department of General Surgery, First Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Xi'an 710061, P.R. China, Department of Emergency, Second Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Xi'an 710004, P.R. China
Published online on: August 7, 2012 https://doi.org/10.3892/etm.2012.657
Pages: 615-620

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Obesity increases the risk of gastric cancer and may affect its development and progression, however, the mechanisms underlying this association are completely unknown. The purpose of the current study was to investigate the effect of obesity on gastric cancer growth by adopting a novel in vivo model. Diet-induced obese and lean mice were inoculated with murine forestomach carcinoma cells, and studied for 2 weeks. Tumor histology, cellular proliferation and apoptosis were evaluated. Serum glucose, insulin, visfatin levels and peripheral CD3+, CD4+/-, CD8+/- lymphocytes were assayed. All mice were alive and developed no metastasis, a greater number of obese mice developed palpable tumors than lean mice. The tumors from obese mice had a larger volume, greater intratumoral adipocyte mass, and exhibited a higher proliferation and reduced apoptosis rate compared to those of lean animals. Both serum insulin and visfatin concentrations correlated positively with tumor proliferation and negatively with tumor apoptosis. Obese mice had a significantly lower level of CD3+, CD3+CD4+ T lymphocytes, and a lower level of CD4+/CD8+ in peripheral blood compared to these lymphocyte levels in the lean mice. In conclusion, the altered adipocytokine milieu and insulin resistance observed in obesity may lead directly to alterations in the tumor microenvironment and cell immunity for avoiding cancer, thereby, promoting gastric cancer survival and growth.

View Figures

View References

1	Parkin DM, Bray F, Ferlay J and Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 55:74–108. 2005. View Article : Google Scholar
2	Brenner H, Rothenbacher D and Arndt V: Epidemiology of stomach cancer. Methods Mol Biol. 472:467–477. 2009. View Article : Google Scholar
3	Forman D and Burley VJ: Gastric cancer: global pattern of the disease and an overview of environmental risk factors. Best Pract Res Clin Gastroenterol. 20:633–649. 2006. View Article : Google Scholar : PubMed/NCBI
4	Flegal KM, Carroll MD, Kit BK and Ogden CL: Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999–2010. JAMA. 307:491–497. 2012.
5	Tilg H and Moschen AR: Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol. 6:772–783. 2006. View Article : Google Scholar : PubMed/NCBI
6	Calle EE and Kaaks R: Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer. 4:579–591. 2004. View Article : Google Scholar : PubMed/NCBI
7	Yang P, Zhou Y, Chen B, Wan HW, Jia GQ, Bai HL and Wu XT: Overweight, obesity and gastric cancer risk: results from a meta-analysis of cohort studies. Eur J Cancer. 45:2867–2873. 2009. View Article : Google Scholar : PubMed/NCBI
8	Yakar S, Nunez NP, Pennisi P, et al: Increased tumor growth in mice with diet-induced obesity: impact of ovarian hormones. Endocrinology. 147:5826–5834. 2006. View Article : Google Scholar : PubMed/NCBI
9	Qian SS, Gao J, Wang JX, Liu Y and Dong HY: Establishment of a mouse forestomach carcinoma cell line (MFC) with spontaneous hematogenous metastasis and preliminary study of its biological characteristics. Zhonghua Zhong Liu Za Zhi. 9:261–264. 1987.(In Chinese).
10	Zyromski NJ, Mathur A, Pitt HA, et al: Obesity potentiates the growth and dissemination of pancreatic cancer. Surgery. 146:258–263. 2009. View Article : Google Scholar : PubMed/NCBI
11	Kitayama J, Tabuchi M, Tsurita G, Ishikawa M, Otani K and Nagawa H: Adiposity and gastrointestinal malignancy. Digestion. 79:26–32. 2009. View Article : Google Scholar
12	Kitayama J, Hatano K, Kaisaki S, Suzuki H, Fujii S and Nagawa H: Hyperlipidaemia is positively correlated with lymph node metastasis in men with early gastric cancer. Br J Surg. 91:191–198. 2004. View Article : Google Scholar
13	Moriwaki Y, Kunisaki C, Kobayashi S, Harada H, Imai S and Kasaoka C: Does body mass index (BMI) influence morbidity and long-term survival in gastric cancer patients after gastrectomy? Hepatogastroenterology. 50:284–288. 2003.PubMed/NCBI
14	Ojima T, Iwahashi M, Nakamori M, et al: Influence of overweight on patients with gastric cancer after undergoing curative gastrectomy: an analysis of 689 consecutive cases managed by a single center. Arch Surg. 144:351–358. 2009. View Article : Google Scholar
15	Payer J, Jackuliak P and Nagyová M: Obesity and a risk of carcinoma. Vnitr Lek. 56:1082–1087. 2010.(In Slovak).
16	Pollak M: Insulin-like growth factor-related signaling and cancer development. Recent Results Cancer Res. 174:49–53. 2007. View Article : Google Scholar : PubMed/NCBI
17	Samal B, Sun Y, Stearns G, Xie C, Suggs S and McNiece I: Cloning and characterization of the cDNA encoding a novel human pre-B-cell colony-enhancing factor. Mol Cell Biol. 14:1431–1437. 1994.PubMed/NCBI
18	Fukuhara A, Matsuda M, Nishizawa M, et al: Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science. 307:426–430. 2005. View Article : Google Scholar : PubMed/NCBI
19	Kim SR, Park HJ, Bae YH, et al: Curcumin down-regulates visfatin expression and inhibits breast cancer cell invasion. Endocrinology. 153:554–563. 2012. View Article : Google Scholar : PubMed/NCBI
20	Kim JG, Kim EO, Jeong BR, et al: Visfatin stimulates proliferation of MCF-7 human breast cancer cells. Mol Cells. 30:341–345. 2010. View Article : Google Scholar : PubMed/NCBI
21	Patel ST, Mistry T, Brown JE, Digby JE, Adya R, Desai KM and Randeva HS: A novel role for the adipokine visfatin/pre-B cell colony-enhancing factor 1 in prostate carcinogenesis. Peptides. 31:51–57. 2010. View Article : Google Scholar : PubMed/NCBI
22	Bi TQ and Che XM: Nampt/PBEF/visfatin and cancer. Cancer Biol Ther. 10:119–125. 2010. View Article : Google Scholar : PubMed/NCBI
23	Reddy PS, Umesh S, Thota B, et al: PBEF1/NAmPRTase/visfatin: a potential malignant astrocytoma/glioblastoma serum marker with prognostic value. Cancer Biol Ther. 7:663–668. 2008. View Article : Google Scholar : PubMed/NCBI
24	Nakajima TE, Yamada Y, Hamano T, et al: Adipocytokine levels in gastric cancer patients: resistin and visfatin as biomarkers of gastric cancer. J Gastroenterol. 44:685–690. 2009. View Article : Google Scholar : PubMed/NCBI
25	Nakajima TE, Yamada Y, Hamano T, et al: Adipocytokines as new promising markers of colorectal tumors: adiponectin for colorectal adenoma, and resistin and visfatin for colorectal cancer. Cancer Sci. 101:1286–1291. 2010. View Article : Google Scholar : PubMed/NCBI
26	Zhang Y, Daquinag A, Traktuev DO, et al: White adipose tissue cells are recruited by experimental tumors and promote cancer progression in mouse models. Cancer Res. 69:5259–5266. 2009. View Article : Google Scholar : PubMed/NCBI
27	Zhang Y, Bellows CF and Kolonin MG: Adipose tissue-derived progenitor cells and cancer. World J Stem Cells. 2:103–113. 2010. View Article : Google Scholar : PubMed/NCBI
28	Comoglio PM and Trusolino L: Cancer: the matrix is now in control. Nat Med. 11:1156–1159. 2005. View Article : Google Scholar : PubMed/NCBI