Adiponectin Receptor-1 Expression is Associated with Good Prognosis in Gastric Cancer

Overview

Journal J Exp Clin Cancer Res

Publisher Biomed Central

Specialty Oncology

Date 2011 Nov 15

PMID 22078265

Citations 19

Authors

Tomoya Tsukada

Sachio Fushida

Shinichi Harada

Shiroh Terai

Yasumichi Yagi

Jun Kinoshita

Katsunobu Oyama

Hidehiro Tajima

Hideto Fujita

Itasu Ninomiya

Takashi Fujimura

Tetsuo Ohta

Affiliations

Soon will be listed here.

Abstract

Background: Adiponectin is inversely related to BMI, positively correlates with insulin sensitivity, and has anti-atherogenic effects. In recent years, adiponectin has been well studied in the field of oncology. Adiponectin has been shown to have antiproliferative effects on gastric cancer, and adiponectin expression is inversely correlated with clinical staging of the disease. However, no studies have reported the correlation between serum adiponectin and receptor expression with disease progression.

Methods: In this study, we evaluated expression levels of 2 adiponectin receptors--AdipoR1 and AdipoR2--and attempted to correlate their expression with prognosis in gastric cancer patients. AdipoR1 and AdipoR2 expression in gastric cancer cell lines (MKN45, TMK-1, NUGC3, and NUGC4) was evaluated by western blotting analysis, and the antiproliferative potential of adiponectin was examined in vitro. Serum adiponectin levels were evaluated in 100 gastric cancer patients, and the expression of AdipoR1 and AdipoR2 was assessed by immunohistochemical staining.

Results: MKN45 and NUGC3 expressed higher levels of AdipoR1 compared to NUGC4, even though there was no significance in AdipoR2 expression. The antiproliferative effect of adiponectin was confirmed in MKN45 and NUGC3 at 10 μg/ml. No significant associations were observed between serum adiponectin levels and clinicopathological characteristics, but lymphatic metastasis and peritoneal dissemination were significantly higher in the negative AdipoR1 immunostaining group (24/32, p = 0.013 and 9/32, p = 0.042, respectively) compared to the positive AdipoR1 group (lymphatic metastasis, 33/68; peritoneal dissemination, 8/68). On the other hand, AdipoR2 expression was only associated with histopathological type (p = 0.001). In survival analysis, the AdipoR1 positive staining group had significantly longer survival rates than the negative staining group (p = 0.01). However, multivariate analysis indicated that AdipoR1 was not an independent prognostic factor on patient's survival on gastric cancer.

Conclusions: In gastric cancer, adiponectin has the possibility to be involved in cell growth suppression via AdipoR1. The presence of AdipoR1 could be a novel anticancer therapeutic target in gastric cancer.

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References

Hara K, Horikoshi M, Yamauchi T, Yago H, Miyazaki O, Ebinuma H . Measurement of the high-molecular weight form of adiponectin in plasma is useful for the prediction of insulin resistance and metabolic syndrome. Diabetes Care. 2006; 29(6):1357-62. DOI: 10.2337/dc05-1801. View

Kerem M, Ferahkose Z, Yilmaz U, Pasaoglu H, Ofluoglu E, Bedirli A . Adipokines and ghrelin in gastric cancer cachexia. World J Gastroenterol. 2008; 14(23):3633-41. PMC: 2719226. DOI: 10.3748/wjg.14.3633. View

Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S . Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature. 2003; 423(6941):762-9. DOI: 10.1038/nature01705. View

Goktas S, Yilmaz M, Caglar K, Sonmez A, Kilic S, Bedir S . Prostate cancer and adiponectin. Urology. 2005; 65(6):1168-72. DOI: 10.1016/j.urology.2004.12.053. View

Otani K, Kitayama J, Kamei T, Soma D, Miyato H, Yamauchi T . Adiponectin receptors are downregulated in human gastric cancer. J Gastroenterol. 2010; 45(9):918-27. DOI: 10.1007/s00535-010-0228-2. View

Barresi V, Grosso M, Giuffre G, Tuccari G, Barresi G . The expression of adiponectin receptors Adipo-R1 and Adipo-R2 is associated with an intestinal histotype and longer survival in gastric carcinoma. J Clin Pathol. 2009; 62(8):705-9. DOI: 10.1136/jcp.2009.066175. View

Jung T, Lee J, Shim W, Kang E, Kim J, Ahn C . Adiponectin protects human neuroblastoma SH-SY5Y cells against acetaldehyde-induced cytotoxicity. Biochem Pharmacol. 2006; 72(5):616-23. DOI: 10.1016/j.bcp.2006.05.013. View

Park M, Youn B, Zheng X, Wu D, Xu A, Sweeney G . Globular adiponectin, acting via AdipoR1/APPL1, protects H9c2 cells from hypoxia/reoxygenation-induced apoptosis. PLoS One. 2011; 6(4):e19143. PMC: 3084258. DOI: 10.1371/journal.pone.0019143. View

Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley R . Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab. 2001; 86(5):1930-5. DOI: 10.1210/jcem.86.5.7463. View

10.

Berg A, Combs T, Du X, Brownlee M, Scherer P . The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat Med. 2001; 7(8):947-53. DOI: 10.1038/90992. View

11.

Ishikawa M, Kitayama J, Yamauchi T, Kadowaki T, Maki T, Miyato H . Adiponectin inhibits the growth and peritoneal metastasis of gastric cancer through its specific membrane receptors AdipoR1 and AdipoR2. Cancer Sci. 2007; 98(7):1120-7. PMC: 11160031. DOI: 10.1111/j.1349-7006.2007.00486.x. View

12.

Japanese Gastric Cancer Association . Japanese Classification of Gastric Carcinoma - 2nd English Edition -. Gastric Cancer. 2002; 1(1):10-24. DOI: 10.1007/s101209800016. View

13.

Ouedraogo R, Wu X, Xu S, Fuchsel L, Motoshima H, Mahadev K . Adiponectin suppression of high-glucose-induced reactive oxygen species in vascular endothelial cells: evidence for involvement of a cAMP signaling pathway. Diabetes. 2006; 55(6):1840-6. DOI: 10.2337/db05-1174. View

14.

Miyoshi Y, Funahashi T, Kihara S, Taguchi T, Tamaki Y, Matsuzawa Y . Association of serum adiponectin levels with breast cancer risk. Clin Cancer Res. 2003; 9(15):5699-704. View

15.

Ishikawa M, Kitayama J, Kazama S, Hiramatsu T, Hatano K, Nagawa H . Plasma adiponectin and gastric cancer. Clin Cancer Res. 2005; 11(2 Pt 1):466-72. View

16.

Chandran M, Phillips S, Ciaraldi T, Henry R . Adiponectin: more than just another fat cell hormone?. Diabetes Care. 2003; 26(8):2442-50. DOI: 10.2337/diacare.26.8.2442. View

17.

Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J . Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun. 1999; 257(1):79-83. DOI: 10.1006/bbrc.1999.0255. View

18.

Kim A, Lee Y, Kim K, Lee J, Lee H, Jang S . Adiponectin represses colon cancer cell proliferation via AdipoR1- and -R2-mediated AMPK activation. Mol Endocrinol. 2010; 24(7):1441-52. PMC: 5417469. DOI: 10.1210/me.2009-0498. View

19.

Daimon M, Oizumi T, Saitoh T, Kameda W, Hirata A, Yamaguchi H . Decreased serum levels of adiponectin are a risk factor for the progression to type 2 diabetes in the Japanese Population: the Funagata study. Diabetes Care. 2003; 26(7):2015-20. DOI: 10.2337/diacare.26.7.2015. View

20.

Spyridopoulos T, Petridou E, Skalkidou A, Dessypris N, Chrousos G, Mantzoros C . Low adiponectin levels are associated with renal cell carcinoma: a case-control study. Int J Cancer. 2007; 120(7):1573-8. DOI: 10.1002/ijc.22526. View