Adiponectin receptors are downregulated in human gastric cancer

Otani, Kensuke; Kitayama, Joji; Kamei, Takao; Soma, Daisuke; Miyato, Hideyo; Yamauchi, Toshimasa; Kadowaki, Takashi; Nagawa, Hirokazu

doi:10.1007/s00535-010-0228-2

Cited by 26 publications

(8 citation statements)

References 59 publications

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“…On the other hand, no clear associations were observed between AdipoR2 expression and any of the clinical characteristics that we evaluated. Otani et al [36] reported that there are no significant associations between AdipoR1 mRNA levels and various pathological features in gastric cancer, whereas Barresi et al reported longer overall survival in patients with positive AdipoR1/R2 expression [37]. Our clinical results reconfirm that AdipoR1 expression inversely correlates with tumor growth and might contributes to improvement of prognosis significantly, but not independently, in gastric cancer patients.…”

Section: Discussionsupporting

confidence: 80%

Adiponectin receptor-1 expression is associated with good prognosis in gastric cancer

Tsukada

Fushida

Harada

et al. 2011

J Exp Clin Cancer Res

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BackgroundAdiponectin 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.MethodsIn 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.ResultsMKN45 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.ConclusionsIn 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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Section: Discussionsupporting

confidence: 80%

Adiponectin receptor-1 expression is associated with good prognosis in gastric cancer

Tsukada

Fushida

Harada

et al. 2011

J Exp Clin Cancer Res

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“…In addition, the expression of adiponectin receptors has been documented in several human cancer cell lines, such as gastric, breast, prostate, and endometrial cancer cells (Barb et al, 2007). An in vitro experiment using two gastric cancer cell lines, MKN-74 and NUGC-3, showed that the expression levels of AdipoR1 and AdipoR2 were significantly decreased by transforming growth factor-b in a dose-dependent manner (Otani et al, 2010). In gastric cancer tissue, as compared to findings in the normal counterparts, AdipoR1 mRNA expression tended to be decreased and AdipoR2 expression was significantly decreased (Ishikawa et al, 2007).…”

Section: Biological Functions Of Adipor In Various Tissuesmentioning

confidence: 99%

Adiponectin Receptor as a Key Player in Healthy Longevity and Obesity-Related Diseases

2013

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Adiponectin is a fat-derived hormone whose reduction plays central roles in obesity-linked diseases including insulin resistance/type 2 diabetes and atherosclerosis. The cloning of Adiponectin receptors AdipoR1 and AdipoR2 has stimulated adiponectin research, revealing pivotal roles for AdipoRs in pleiotropic adiponectin actions, as well as some postreceptor signaling mechanisms. Adiponectin signaling has thus become one of the major research fields in metabolism and clinical medicine. Studies on AdipoRs will further our understanding of the role of adiponectin in obesity-linked diseases and shortened life span and may guide the design of antidiabetic and antiaging drugs with AdipoR as a target.

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“…In a previous study by Otani et al (39), using quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical staining, it was demonstrated that the expression of AdipoR2 was significantly decreased in gastric cancer tissues compared to normal colorectal tissue. In addition, AdipoR1 levels tended to be decreased.…”

Section: Introductionmentioning

confidence: 99%

Adiponectin receptor 2 is negatively associated with lymph node metastasis of colorectal cancer

Hiyoshi¹

2012

Oncol Lett

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Abstract. Adiponectin is a hormone secreted by adipose tissue and has a variety of functions including the inhibition of tumor growth. The expression and function of the two major adiponectin receptors, AdipoR1 and AdipoR2, in malignant tissue have not been well characterized. In the present study, we evaluated the mRNA levels of AdipoR1 and AdipoR2 expression in 48 surgically resected colorectal cancer specimens, as well as normal colonic mucosa, by quantitative RT-PCR. The values obtained were standardized by β-actin mRNA, and the correlation between their relative expression levels and the clinicopathological characteristics of the patients was examined. The relative expression levels of AdipoR1 and AdipoR2 were significantly reduced in cancer tissue compared with normal tissue (AdipoR1: 0.97±0.39 vs. 1.37±0.41, P<0.0001; AdipoR2: 0.92±0.31 vs. 1.60±0.46, P<0.0001). AdipoR1 and AdipoR2 levels were further reduced in tumors with nodal metastases and the difference was statistically significant in the case of AdipoR2 (0.79±0.27 vs. 1.02±0.30, P=0.012). The results of this study demonstrated that the expression levels of adiponectin receptors are reduced in cancer specimens compared to normal tissue, indicating a downregulation in the course of the development and progression of colorectal cancer. Since adiponectin is abundantly present in the whole body and has inhibitory effects on cancer cells, this downregulation of the receptors may be an escape mechanism of malignant cells from the suppressive effects of adiponectin.

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Adiponectin receptors are downregulated in human gastric cancer

Cited by 26 publications

References 59 publications

Adiponectin receptor-1 expression is associated with good prognosis in gastric cancer

Adiponectin receptor-1 expression is associated with good prognosis in gastric cancer

Adiponectin Receptor as a Key Player in Healthy Longevity and Obesity-Related Diseases

Adiponectin receptor 2 is negatively associated with lymph node metastasis of colorectal cancer

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